Wnts and the hallmarks of cancer

1.

Srivastava, M., Begovic, E., Chapman, J., Putnam, N. H., Hellsten, U., Kawashima, T., et al. (2008). The Trichoplax genome and the nature of placozoans. Nature, 454(7207), 955–960. https://doi.org/10.1038/nature07191.CrossRefPubMed

2.

Nichols, S. A., Dirks, W., Pearse, J. S., & King, N. (2006). Early evolution of animal cell signaling and adhesion genes. Proceedings of the National Academy of Sciences of the United States of America, 103(33), 12451–12456. https://doi.org/10.1073/pnas.0604065103.CrossRefPubMedPubMedCentral

3.

Loh, K. M., van Amerongen, R., & Nusse, R. (2016). Generating cellular diversity and spatial form: Wnt signaling and the evolution of multicellular animals. Developmental Cell, 38(6), 643–655. https://doi.org/10.1016/j.devcel.2016.08.011.CrossRefPubMed

4.

Nusse, R., & Varmus, H. E. (1982). Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 31(1), 99–109.CrossRefPubMed

5.

Aoki, K., & Taketo, M. M. (2007). Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. Journal of Cell Science, 120(Pt 19), 3327–3335. https://doi.org/10.1242/jcs.03485.CrossRefPubMed

6.

Yu, J., & Virshup, D. M. (2014). Updating the Wnt pathways. Bioscience Reports, 34(5). https://doi.org/10.1042/BSR20140119.

7.

Steinhart, Z., & Angers, S. (2018). Wnt signaling in development and tissue homeostasis. Development, 145(11), dev146589. https://doi.org/10.1242/dev.146589.CrossRefPubMed

8.

Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70. https://doi.org/10.1016/s0092-8674(00)81683-9.CrossRefPubMed

9.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMed

10.

Obaya, A. J., & Sedivy, J. M. (2002). Regulation of cyclin-Cdk activity in mammalian cells. Cellular and Molecular Life Sciences, 59(1), 126–142. https://doi.org/10.1007/s00018-002-8410-1.CrossRefPubMed

11.

Massagué, J. (2004). G1 cell-cycle control and cancer. Nature, 432(7015), 298–306. https://doi.org/10.1038/nature03094.CrossRefPubMed

12.

Niehrs, C., & Acebron, S. P. (2012). Mitotic and mitogenic Wnt signalling. The EMBO Journal, 31(12), 2705–2713. https://doi.org/10.1038/emboj.2012.124.CrossRefPubMedPubMedCentral

13.

He, T. C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., et al. (1998). Identification of c-MYC as a target of the APC pathway. Science, 281(5382), 1509–1512. https://doi.org/10.1126/science.281.5382.1509.CrossRefPubMed

14.

Tetsu, O., & McCormick, F. (1999). Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature, 398(6726), 422–426. https://doi.org/10.1038/18884.CrossRefPubMed

15.

Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D'Amico, M., Pestell, R., & Ben-Ze'ev, A. (1999). The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proceedings of the National Academy of Sciences of the United States of America, 96(10), 5522–5527. https://doi.org/10.1073/pnas.96.10.5522.CrossRefPubMedPubMedCentral

16.

Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998). Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes & Development, 12(22), 3499–3511. https://doi.org/10.1101/gad.12.22.3499.CrossRef

17.

Welcker, M., Singer, J., Loeb, K. R., Grim, J., Bloecher, A., Gurien-West, M., et al. (2003). Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Molecular Cell, 12(2), 381–392. https://doi.org/10.1016/s1097-2765(03)00287-9.CrossRefPubMed

18.

Welcker, M., Orian, A., Jin, J., Grim, J. E., Grim, J. A., Harper, J. W., et al. (2004). The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proceedings of the National Academy of Sciences of the United States of America, 101(24), 9085–9090. https://doi.org/10.1073/pnas.0402770101.CrossRefPubMedPubMedCentral

19.

Acebron, S. P., Karaulanov, E., Berger, B. S., Huang, Y.-L., & Niehrs, C. (2014). Mitotic wnt signaling promotes protein stabilization and regulates cell size. Molecular Cell, 54(4), 663–674. https://doi.org/10.1016/j.molcel.2014.04.014.CrossRefPubMed

20.

Reya, T., & Clevers, H. (2005). Wnt signalling in stem cells and cancer. Nature, 434(7035), 843–850. https://doi.org/10.1038/nature03319.CrossRefPubMed

21.

Leung, C., Tan, S. H., & Barker, N. (2018). Recent advances in Lgr5+ stem cell research. Trends in Cell Biology, 28(5), 380–391. https://doi.org/10.1016/j.tcb.2018.01.010.CrossRefPubMed

22.

Orford, K. W., & Scadden, D. T. (2008). Deconstructing stem cell self-renewal: Genetic insights into cell-cycle regulation. Nature reviews Genetics, 9(2), 115–128. https://doi.org/10.1038/nrg2269.

23.

Kabiri, Z., Greicius, G., Zaribafzadeh, H., Hemmerich, A., Counter, C. M., & Virshup, D. M. (2018). Wnt signaling suppresses MAPK-driven proliferation of intestinal stem cells. The Journal of Clinical Investigation, 128(9). https://doi.org/10.1172/JCI99325.

24.

Riemer, P., Sreekumar, A., Reinke, S., Rad, R., Schäfer, R., Sers, C., et al. (2015). Transgenic expression of oncogenic BRAF induces loss of stem cells in the mouse intestine, which is antagonized by β-catenin activity. Oncogene, 34(24), 3164–3175. https://doi.org/10.1038/onc.2014.247.CrossRefPubMed

25.

Zhong, Z., & Virshup, D. M. (2020). Wnt signaling and drug resistance in cancer. Molecular Pharmacology, 97(2), 72–89. https://doi.org/10.1124/mol.119.117978.CrossRefPubMed

26.

Proffitt, K. D., Madan, B., Ke, Z., Pendharkar, V., Ding, L., Lee, M. A., et al. (2013). Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Research, 73(2), 502–507. https://doi.org/10.1158/0008-5472.CAN-12-2258.CrossRefPubMed

27.

Koo, B.-K., van Es, J. H., van den Born, M., & Clevers, H. (2015). Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia. Proceedings of the National Academy of Sciences of the United States of America, 201508113. https://doi.org/10.1073/pnas.1508113112.

28.

Boulter, L., Guest, R. V., Kendall, T. J., Wilson, D. H., Wojtacha, D., Robson, A. J., et al. (2015). WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. The Journal of Clinical Investigation, 125(3), 1269–1285. https://doi.org/10.1172/JCI76452.CrossRefPubMedPubMedCentral

29.

Storm, E. E., Durinck, S., de Sousa e Melo, F., Tremayne, J., Kljavin, N., Tan, C., et al. (2016). Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature, 529(7584), 97–100. https://doi.org/10.1038/nature16466.CrossRefPubMed

30.

Madan, B., Harmston, N., Nallan, G., Montoya, A., Faull, P., Petretto, E., & Virshup, D. M. (2018). Temporal dynamics of Wnt-dependent transcriptome reveal an oncogenic Wnt/MYC/ribosome axis. The Journal of Clinical Investigation, 128(12), 5620–5633. https://doi.org/10.1172/JCI122383.CrossRefPubMedPubMedCentral

31.

Lin, C. Y., Lovén, J., Rahl, P. B., Paranal, R. M., Burge, C. B., Bradner, J. E., et al. (2012). Transcriptional amplification in tumor cells with elevated c-Myc. Cell, 151(1), 56–67. https://doi.org/10.1016/j.cell.2012.08.026.CrossRefPubMedPubMedCentral

32.

Nie, Z., Hu, G., Wei, G., Cui, K., Yamane, A., Resch, W., et al. (2012). c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell, 151(1), 68–79. https://doi.org/10.1016/j.cell.2012.08.033.CrossRefPubMedPubMedCentral

33.

Bretones, G., Delgado, M. D., & León, J. (2015). Myc and cell cycle control. Biochimica et Biophysica Acta, 1849(5), 506–516. https://doi.org/10.1016/j.bbagrm.2014.03.013.CrossRefPubMed

34.

van Riggelen, J., Yetil, A., & Felsher, D. W. (2010). MYC as a regulator of ribosome biogenesis and protein synthesis. Nature Reviews. Cancer, 10(4), 301–309. https://doi.org/10.1038/nrc2819.CrossRefPubMed

35.

Dang, C. V. (2013). MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harbor Perspectives in Medicine, 3(8), a014217–a014217. https://doi.org/10.1101/cshperspect.a014217.CrossRefPubMedPubMedCentral

36.

Wahlström, T., & Henriksson, M. A. (2015). Impact of MYC in regulation of tumor cell metabolism. Biochimica et Biophysica Acta, 1849(5), 563–569. https://doi.org/10.1016/j.bbagrm.2014.07.004.CrossRefPubMed

37.

Sansom, O. J., Meniel, V. S., Muncan, V., Phesse, T. J., Wilkins, J. A., Reed, K. R., et al. (2007). Myc deletion rescues Apc deficiency in the small intestine. Nature, 446(7136), 676–679. https://doi.org/10.1038/nature05674.CrossRefPubMed

38.

Meyers, R. M., Bryan, J. G., McFarland, J. M., Weir, B. A., Sizemore, A. E., Xu, H., et al. (2017). Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells. Nature Genetics, 49(12), 1779–1784. https://doi.org/10.1038/ng.3984.CrossRefPubMedPubMedCentral

39.

McDonald, E. R., de Weck, A., Schlabach, M. R., Billy, E., Mavrakis, K. J., Hoffman, G. R., et al. (2017). Project DRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell, 170(3), 577–592.e10. https://doi.org/10.1016/j.cell.2017.07.005.CrossRefPubMed

40.

Behan, F. M., Iorio, F., Picco, G., Gonçalves, E., Beaver, C. M., Migliardi, G., et al. (2019). Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature, 31, 1806. https://doi.org/10.1038/s41586-019-1103-9.CrossRef

41.

Fong, C. Y., Gilan, O., Lam, E. Y. N., Rubin, A. F., Ftouni, S., Tyler, D., et al. (2015). BET inhibitor resistance emerges from leukaemia stem cells. Nature, 525(7570), 538–542. https://doi.org/10.1038/nature14888.CrossRefPubMedPubMedCentral

42.

Rathert, P., Roth, M., Neumann, T., Muerdter, F., Roe, J.-S., Muhar, M., et al. (2015). Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature, 525(7570), 543–547. https://doi.org/10.1038/nature14898.CrossRefPubMedPubMedCentral

43.

Harbour, J. W., & Dean, D. C. (2000). Rb function in cell-cycle regulation and apoptosis. Nature Cell Biology, 2(4), E65–E67. https://doi.org/10.1038/35008695.CrossRefPubMed

44.

Giacinti, C., & Giordano, A. (2006). RB and cell cycle progression. Oncogene, 25(38), 5220–5227. https://doi.org/10.1038/sj.onc.1209615.CrossRefPubMed

45.

Henley, S. A., & Dick, F. A. (2012). The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle. Cell Division, 7(1), 10–14. https://doi.org/10.1186/1747-1028-7-10.CrossRefPubMedPubMedCentral

46.

Ohtani, K., DeGregori, J., & Nevins, J. R. (1995). Regulation of the cyclin E gene by transcription factor E2F1. Proceedings of the National Academy of Sciences of the United States of America, 92(26), 12146–12150. https://doi.org/10.1073/pnas.92.26.12146.CrossRefPubMedPubMedCentral

47.

Bracken, A. P., Ciro, M., Cocito, A., & Helin, K. (2004). E2F target genes: unraveling the biology. Trends in Biochemical Sciences, 29(8), 409–417. https://doi.org/10.1016/j.tibs.2004.06.006.CrossRefPubMed

48.

Delmas, V., Beermann, F., Martinozzi, S., Carreira, S., Ackermann, J., Kumasaka, M., et al. (2007). Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes & Development, 21(22), 2923–2935. https://doi.org/10.1101/gad.450107.CrossRef

49.

Jiang, X., Hao, H.-X., Growney, J. D., Woolfenden, S., Bottiglio, C., Ng, N., et al. (2013). Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 110(31), 12649–12654. https://doi.org/10.1073/pnas.1307218110.CrossRefPubMedPubMedCentral

50.

Zhong, Z., Sepramaniam, S., Chew, X. H., Wood, K., Lee, M. A., Madan, B., & Virshup, D. M. (2019). PORCN inhibition synergizes with PI3K/mTOR inhibition in Wnt-addicted cancers. Oncogene, 67(12), 7. https://doi.org/10.1038/s41388-019-0908-1.CrossRef

51.

Visvader, J. E., & Lindeman, G. J. (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nature Reviews. Cancer, 8(10), 755–768. https://doi.org/10.1038/nrc2499.CrossRefPubMed

52.

Chang, J. C. (2016). Cancer stem cells: role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine, 95(1 Suppl 1), S20–S25. https://doi.org/10.1097/MD.0000000000004766.CrossRefPubMedPubMedCentral

53.

Peitzsch, C., Tyutyunnykova, A., Pantel, K., & Dubrovska, A. (2017). Cancer stem cells: the root of tumor recurrence and metastases. Seminars in Cancer Biology, 44, 10–24. https://doi.org/10.1016/j.semcancer.2017.02.011.CrossRefPubMed

54.

Madan, B., Ke, Z., Harmston, N., Ho, S. Y., Frois, A. O., Alam, J., et al. (2016). Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene, 35(17), 2197–2207. https://doi.org/10.1038/onc.2015.280.CrossRefPubMed

55.

Steinhart, Z., Pavlovic, Z., Chandrashekhar, M., Hart, T., Wang, X., Zhang, X., et al. (2017). Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nature Medicine, 23(1), 60–68. https://doi.org/10.1038/nm.4219.CrossRefPubMed

56.

Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., et al. (2017). Senescence-associated reprogramming promotes cancer stemness. Nature, 15, 482. https://doi.org/10.1038/nature25167.CrossRef

57.

White, E., & DiPaola, R. S. (2009). The double-edged sword of autophagy modulation in cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15(17), 5308–5316. https://doi.org/10.1158/1078-0432.CCR-07-5023.CrossRef

58.

Chen, S., Guttridge, D. C., You, Z., Zhang, Z., Fribley, A., Mayo, M. W., et al. (2001). Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription. The Journal of Cell Biology, 152(1), 87–96. https://doi.org/10.1083/jcb.152.1.87.CrossRefPubMedPubMedCentral

59.

Xie, H., Huang, Z., Sadim, M. S., & Sun, Z. (2005). Stabilized beta-catenin extends thymocyte survival by up-regulating Bcl-xL. The Journal of Immunology, 175(12), 7981–7988. https://doi.org/10.4049/jimmunol.175.12.7981.CrossRefPubMed

60.

Melkonyan, H. S., Chang, W. C., Shapiro, J. P., Mahadevappa, M., Fitzpatrick, P. A., Kiefer, M. C., et al. (1997). SARPs: a family of secreted apoptosis-related proteins. Proceedings of the National Academy of Sciences of the United States of America, 94(25), 13636–13641. https://doi.org/10.1073/pnas.94.25.13636.CrossRefPubMedPubMedCentral

61.

Roth, W., Wild-Bode, C., Platten, M., Grimmel, C., Melkonyan, H. S., Dichgans, J., & Weller, M. (2000). Secreted frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells. Oncogene, 19(37), 4210–4220. https://doi.org/10.1038/sj.onc.1203783.CrossRefPubMed

62.

Han, X., & Amar, S. (2004). Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide-induced apoptosis. The Journal of Biological Chemistry, 279(4), 2832–2840. https://doi.org/10.1074/jbc.M308102200.CrossRefPubMed

63.

Uren, A., Reichsman, F., Anest, V., Taylor, W. G., Muraiso, K., Bottaro, D. P., et al. (2000). Secreted frizzled-related protein-1 binds directly to wingless and is a biphasic modulator of Wnt signaling. The Journal of Biological Chemistry, 275(6), 4374–4382. https://doi.org/10.1074/jbc.275.6.4374.CrossRefPubMed

64.

Levine, B., & Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell, 132(1), 27–42. https://doi.org/10.1016/j.cell.2007.12.018.CrossRefPubMedPubMedCentral

65.

Sánchez-Martín, P., & Komatsu, M. (2018). p62/SQSTM1 - steering the cell through health and disease. Journal of Cell Science, 131(21), jcs222836. https://doi.org/10.1242/jcs.222836.CrossRefPubMed

66.

Lee, Y.-K., & Lee, J.-A. (2016). Role of the mammalian ATG8/LC3 family in autophagy: differential and compensatory roles in the spatiotemporal regulation of autophagy. BMB Reports, 49(8), 424–430. https://doi.org/10.5483/bmbrep.2016.49.8.081.CrossRefPubMedPubMedCentral

67.

Gao, C., Cao, W., Bao, L., Zuo, W., Xie, G., Cai, T., et al. (2010). Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nature Cell Biology, 12(8), 781–790. https://doi.org/10.1038/ncb2082.CrossRefPubMed

68.

Petherick, K. J., Williams, A. C., Lane, J. D., Ordóñez-Morán, P., Huelsken, J., Collard, T. J., et al. (2013). Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. The EMBO Journal, 32(13), 1903–1916. https://doi.org/10.1038/emboj.2013.123.CrossRefPubMedPubMedCentral

69.

Luo, X., Ye, S., Jiang, Q., Gong, Y., Yuan, Y., Hu, X., et al. (2018). Wnt inhibitory factor-1-mediated autophagy inhibits Wnt/β-catenin signaling by downregulating dishevelled-2 expression in non-small cell lung cancer cells. International Journal of Oncology, 53(2), 904–914. https://doi.org/10.3892/ijo.2018.4442.CrossRefPubMed

70.

Colella, B., Faienza, F., Carinci, M., D'Alessandro, G., Catalano, M., Santoro, A., et al. (2019). Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells. Cellular Signalling, 53, 357–364. https://doi.org/10.1016/j.cellsig.2018.10.017.CrossRefPubMed

71.

Nàger, M., Sallán, M. C., Visa, A., Pushparaj, C., Santacana, M., Macià, A., et al. (2018). Inhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers. Autophagy, 14(4), 619–636. https://doi.org/10.1080/15548627.2017.1423439.CrossRefPubMedPubMedCentral

72.

Low, K. C., & Tergaonkar, V. (2013). Telomerase: central regulator of all of the hallmarks of cancer. Trends in Biochemical Sciences, 38(9), 426–434. https://doi.org/10.1016/j.tibs.2013.07.001.CrossRefPubMed

73.

Tang, R., Cheng, A. J., Wang, J. Y., & Wang, T. C. (1998). Close correlation between telomerase expression and adenomatous polyp progression in multistep colorectal carcinogenesis. Cancer Research, 58(18), 4052–4054.PubMed

74.

Tahara, H., Kuniyasu, H., Yokozaki, H., Yasui, W., Shay, J. W., Ide, T., & Tahara, E. (1995). Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 1(11), 1245–1251.

75.

Mizumoto, I., Ogawa, Y., Niiyama, H., Nagai, E., Sato, I., Urashima, T., et al. (2001). Possible role of telomerase activation in the multistep tumor progression of periampullary lesions in patients with familial adenomatous polyposis. The American Journal of Gastroenterology, 96(4), 1261–1265. https://doi.org/10.1111/j.1572-0241.2001.03710.x.CrossRefPubMed

76.

Hoffmeyer, K., Raggioli, A., Rudloff, S., Anton, R., Hierholzer, A., Del Valle, I., et al. (2012). Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science, 336(6088), 1549–1554. https://doi.org/10.1126/science.1218370.CrossRefPubMed

77.

Zhang, Y., Toh, L., Lau, P., & Wang, X. (2012). Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer. The Journal of Biological Chemistry, 287(39), 32494–32511. https://doi.org/10.1074/jbc.M112.368282.CrossRefPubMedPubMedCentral

78.

Wang, J., Xie, L. Y., Allan, S., Beach, D., & Hannon, G. J. (1998). Myc activates telomerase. Genes & Development, 12(12), 1769–1774. https://doi.org/10.1101/gad.12.12.1769.CrossRef

79.

Strong, M. A., Vidal-Cardenas, S. L., Karim, B., Yu, H., Guo, N., & Greider, C. W. (2011). Phenotypes in mTERT⁺/⁻ and mTERT⁻/⁻ mice are due to short telomeres, not telomere-independent functions of telomerase reverse transcriptase. Molecular and Cellular Biology, 31(12), 2369–2379. https://doi.org/10.1128/MCB.05312-11.CrossRefPubMedPubMedCentral

80.

Listerman, I., Gazzaniga, F. S., & Blackburn, E. H. (2014). An investigation of the effects of the core protein telomerase reverse transcriptase on Wnt signaling in breast cancer cells. Molecular and Cellular Biology, 34(2), 280–289. https://doi.org/10.1128/MCB.00844-13.CrossRefPubMedPubMedCentral

81.

Yang, T.-L. B., Chen, Q., Deng, J. T., Jagannathan, G., Tobias, J. W., Schultz, D. C., et al. (2017). Mutual reinforcement between telomere capping and canonical Wnt signalling in the intestinal stem cell niche. Nature Communications, 8(1), 14766–14710. https://doi.org/10.1038/ncomms14766.CrossRefPubMedPubMedCentral

82.

Wilson, C. L., Heppner, K. J., Labosky, P. A., Hogan, B. L., & Matrisian, L. M. (1997). Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proceedings of the National Academy of Sciences of the United States of America, 94(4), 1402–1407. https://doi.org/10.1073/pnas.94.4.1402.CrossRefPubMedPubMedCentral

83.

Brabletz, T., Jung, A., Dag, S., Hlubek, F., & Kirchner, T. (1999). Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. The American Journal of Pathology, 155(4), 1033–1038. https://doi.org/10.1016/s0002-9440(10)65204-2.CrossRefPubMedPubMedCentral

84.

Lévy, L., Neuveut, C., Renard, C.-A., Charneau, P., Branchereau, S., Gauthier, F., et al. (2002). Transcriptional activation of interleukin-8 by beta-catenin-Tcf4. The Journal of Biological Chemistry, 277(44), 42386–42393. https://doi.org/10.1074/jbc.M207418200.CrossRefPubMed

85.

Li, A., Dubey, S., Varney, M. L., Dave, B. J., & Singh, R. K. (2003). IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. The Journal of Immunology, 170(6), 3369–3376. https://doi.org/10.4049/jimmunol.170.6.3369.CrossRefPubMed

86.

Ferrara, N., Hillan, K. J., Gerber, H.-P., & Novotny, W. (2004). Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nature Reviews Drug Discovery, 3(5), 391–400. https://doi.org/10.1038/nrd1381.CrossRefPubMed

87.

Krock, B. L., Skuli, N., & Simon, M. C. (2011). Hypoxia-induced angiogenesis: good and evil. Genes & Cancer, 2(12), 1117–1133. https://doi.org/10.1177/1947601911423654.CrossRef

88.

Zhang, X., Gaspard, J. P., & Chung, D. C. (2001). Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia. Cancer Research, 61(16), 6050–6054.PubMed

89.

Easwaran, V., Lee, S. H., Inge, L., Guo, L., Goldbeck, C., Garrett, E., et al. (2003). Beta-catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Research, 63(12), 3145–3153.PubMed

90.

Posokhova, E., Shukla, A., Seaman, S., Volate, S., Hilton, M. B., Wu, B., et al. (2015). GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Reports, 10(2), 123–130. https://doi.org/10.1016/j.celrep.2014.12.020.CrossRefPubMed

91.

Chang, J., Mancuso, M. R., Maier, C., Liang, X., Yuki, K., Yang, L., et al. (2017). Gpr124 is essential for blood-brain barrier integrity in central nervous system disease. Nature Medicine, 23(4), 450–460. https://doi.org/10.1038/nm.4309.CrossRefPubMedPubMedCentral

92.

Cho, C., Smallwood, P. M., & Nathans, J. (2017). Reck and Gpr124 are essential receptor cofactors for Wnt7a/Wnt7b-specific signaling in mammalian CNS angiogenesis and blood-brain barrier regulation. Neuron, 95(5), 1056–1073.e5. https://doi.org/10.1016/j.neuron.2017.07.031.CrossRefPubMedPubMedCentral

93.

Chaffer, C. L., & Weinberg, R. A. (2011). A perspective on cancer cell metastasis. Science, 331(6024), 1559–1564. https://doi.org/10.1126/science.1203543.CrossRefPubMed

94.

Fischer, K. R., Durrans, A., Lee, S., Sheng, J., Li, F., Wong, S. T. C., et al. (2015). Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature, 527(7579), 472–476. https://doi.org/10.1038/nature15748.CrossRefPubMedPubMedCentral

95.

Zheng, X., Carstens, J. L., Kim, J., Scheible, M., Kaye, J., Sugimoto, H., et al. (2015). Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature, 527(7579), 525–530. https://doi.org/10.1038/nature16064.CrossRefPubMedPubMedCentral

96.

Somarelli, J. A., Schaeffer, D., Marengo, M. S., Bepler, T., Rouse, D., Ware, K. E., et al. (2016). Distinct routes to metastasis: plasticity-dependent and plasticity-independent pathways. Oncogene. https://doi.org/10.1038/onc.2015.497.

97.

Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017). Emerging biological principles of metastasis. Cell, 168(4), 670–691. https://doi.org/10.1016/j.cell.2016.11.037.CrossRefPubMedPubMedCentral

98.

Brabletz, T., Jung, A., Hermann, K., Günther, K., Hohenberger, W., & Kirchner, T. (1998). Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathology, Research and Practice, 194(10), 701–704. https://doi.org/10.1016/s0344-0338(98)80129-5.CrossRefPubMed

99.

Brabletz, T., Jung, A., Reu, S., Porzner, M., Hlubek, F., Kunz-Schughart, L. A., et al. (2001). Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10356–10361. https://doi.org/10.1073/pnas.171610498.CrossRefPubMedPubMedCentral

100.

Vermeulen, L., de Sousa e Melo, F., van der Heijden, M., Cameron, K., de Jong, J. H., Borovski, T., et al. (2010). Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature Cell Biology, 12(5), 468–476. https://doi.org/10.1038/ncb2048.CrossRefPubMed

101.

Maruyama, K., Ochiai, A., Akimoto, S., Nakamura, S., Baba, S., Moriya, Y., & Hirohashi, S. (2000). Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer. Oncology, 59(4), 302–309. https://doi.org/10.1159/000012187.CrossRefPubMed

102.

Hörkkö, T. T., Klintrup, K., Mäkinen, J. M., Näpänkangas, J. B., Tuominen, H. J., Mäkelä, J., et al. (2006). Budding invasive margin and prognosis in colorectal cancer--no direct association with beta-catenin expression. European Journal of Cancer, 42(7), 964–971. https://doi.org/10.1016/j.ejca.2006.01.017.CrossRefPubMed

103.

Horst, D., Reu, S., Kriegl, L., Engel, J., Kirchner, T., & Jung, A. (2009). The intratumoral distribution of nuclear beta-catenin is a prognostic marker in colon cancer. Cancer, 115(10), 2063–2070. https://doi.org/10.1002/cncr.24254.CrossRefPubMed

104.

Gao, Z.-H., Lu, C., Wang, M.-X., Han, Y., & Guo, L.-J. (2014). Differential β-catenin expression levels are associated with morphological features and prognosis of colorectal cancer. Oncology Letters, 8(5), 2069–2076. https://doi.org/10.3892/ol.2014.2433.CrossRefPubMedPubMedCentral

105.

Liu, L., Zhu, X.-D., Wang, W.-Q., Shen, Y., Qin, Y., Ren, Z.-G., et al. (2010). Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 16(10), 2740–2750. https://doi.org/10.1158/1078-0432.CCR-09-2610.CrossRef

106.

Yook, J. I., Li, X.-Y., Ota, I., Fearon, E. R., & Weiss, S. J. (2005). Wnt-dependent regulation of the E-cadherin repressor snail. The Journal of Biological Chemistry, 280(12), 11740–11748. https://doi.org/10.1074/jbc.M413878200.CrossRefPubMed

107.

Esposito, M., Mondal, N., Greco, T. M., Wei, Y., Spadazzi, C., Lin, S.-C., et al. (2019). Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nature Cell Biology, 21(5), 627–639. https://doi.org/10.1038/s41556-019-0309-2.CrossRefPubMedPubMedCentral

108.

Nandana, S., Tripathi, M., Duan, P., Chu, C.-Y., Mishra, R., Liu, C., et al. (2017). Bone metastasis of prostate cancer can be therapeutically targeted at the TBX2-WNT signaling axis. Cancer Research, 77(6), 1331–1344. https://doi.org/10.1158/0008-5472.CAN-16-0497.CrossRefPubMedPubMedCentral

109.

Nguyen, D. X., Chiang, A. C., Zhang, X. H.-F., Kim, J. Y., Kris, M. G., Ladanyi, M., et al. (2009). WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell, 138(1), 51–62. https://doi.org/10.1016/j.cell.2009.04.030.CrossRefPubMedPubMedCentral

110.

Han, F., Liu, W.-B., Shi, X.-Y., Yang, J.-T., Zhang, X., Li, Z.-M., et al. (2018). SOX30 inhibits tumor metastasis through attenuating Wnt-signaling via transcriptional and posttranslational regulation of β-catenin in lung cancer. EBioMedicine, 31, 253–266. https://doi.org/10.1016/j.ebiom.2018.04.026.CrossRefPubMedPubMedCentral

111.

Cai, J., Fang, L., Huang, Y., Li, R., Xu, X., Hu, Z., et al. (2017). Simultaneous overactivation of Wnt/β-catenin and TGFβ signalling by miR-128-3p confers chemoresistance-associated metastasis in NSCLC. Nature Communications, 8(1), 15870–15819. https://doi.org/10.1038/ncomms15870.CrossRefPubMedPubMedCentral

112.

Dai, F.-Q., Li, C.-R., Fan, X.-Q., Tan, L., Wang, R.-T., & Jin, H. (2019). miR-150-5p inhibits non-small-cell lung cancer metastasis and recurrence by targeting HMGA2 and β-catenin signaling. Molecular Therapy--Nucleic Acids, 16, 675–685. https://doi.org/10.1016/j.omtn.2019.04.017.CrossRefPubMedPubMedCentral

113.

Wellenstein, M. D., Coffelt, S. B., Duits, D. E. M., van Miltenburg, M. H., Slagter, M., de Rink, I., et al. (2019). Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature, 15, e493. https://doi.org/10.1038/s41586-019-1450-6.CrossRef

114.

Tenbaum, S. P., Ordóñez-Morán, P., Puig, I., Chicote, I., Arqués, O., Landolfi, S., et al. (2012). β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nature Medicine, 18(6), 892–901. https://doi.org/10.1038/nm.2772.CrossRefPubMed

115.

Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., et al. (2012). Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell, 151(7), 1542–1556. https://doi.org/10.1016/j.cell.2012.11.024.CrossRefPubMed

116.

Yu, M., Ting, D. T., Stott, S. L., Wittner, B. S., Ozsolak, F., Paul, S., et al. (2012). RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature, 487(7408), 510–513. https://doi.org/10.1038/nature11217.CrossRefPubMedPubMedCentral

117.

Miyamoto, D. T., Zheng, Y., Wittner, B. S., Lee, R. J., Zhu, H., Broderick, K. T., et al. (2015). RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science, 349(6254), 1351–1356. https://doi.org/10.1126/science.aab0917.CrossRefPubMedPubMedCentral

118.

Li, F., Tiede, B., Massagué, J., & Kang, Y. (2007). Beyond tumorigenesis: cancer stem cells in metastasis. Cell Research, 17(1), 3–14. https://doi.org/10.1038/sj.cr.7310118.CrossRefPubMed

119.

Shiozawa, Y., Nie, B., Pienta, K. J., Morgan, T. M., & Taichman, R. S. (2013). Cancer stem cells and their role in metastasis. Pharmacology & Therapeutics, 138(2), 285–293. https://doi.org/10.1016/j.pharmthera.2013.01.014.CrossRef

120.

Alexandrov, L. B., Kim, J., Haradhvala, N. J., Huang, M. N., Tian Ng, A. W., Wu, Y., et al. (2020). The repertoire of mutational signatures in human cancer. Nature, 578(7793), 94–101. https://doi.org/10.1038/s41586-020-1943-3.CrossRefPubMedPubMedCentral

121.

Rusan, N. M., & Peifer, M. (2008). Original CIN: reviewing roles for APC in chromosome instability. The Journal of Cell Biology, 181(5), 719–726. https://doi.org/10.1083/jcb.200802107.CrossRefPubMedPubMedCentral

122.

Näthke, I. S. (2004). The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annual Review of Cell and Developmental Biology, 20(1), 337–366. https://doi.org/10.1146/annurev.cellbio.20.012103.094541.CrossRefPubMed

123.

Munemitsu, S., Souza, B., Müller, O., Albert, I., Rubinfeld, B., & Polakis, P. (1994). The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Research, 54(14), 3676–3681.PubMed

124.

Smith, K. J., Levy, D. B., Maupin, P., Pollard, T. D., Vogelstein, B., & Kinzler, K. W. (1994). Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Research, 54(14), 3672–3675.PubMed

125.

Zumbrunn, J., Kinoshita, K., Hyman, A. A., & Näthke, I. S. (2001). Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Current Biology: CB, 11(1), 44–49. https://doi.org/10.1016/s0960-9822(01)00002-1.CrossRefPubMed

126.

Fodde, R., Kuipers, J., Rosenberg, C., Smits, R., Kielman, M., Gaspar, C., et al. (2001). Mutations in the APC tumour suppressor gene cause chromosomal instability. Nature Cell Biology, 3(4), 433–438. https://doi.org/10.1038/35070129.CrossRefPubMed

127.

Banks, J. D., & Heald, R. (2004). Adenomatous polyposis coli associates with the microtubule-destabilizing protein XMCAK. Current Biology: CB, 14(22), 2033–2038. https://doi.org/10.1016/j.cub.2004.10.049.CrossRefPubMed

128.

Tighe, A., Johnson, V. L., & Taylor, S. S. (2004). Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability. Journal of Cell Science, 117(Pt 26), 6339–6353. https://doi.org/10.1242/jcs.01556.CrossRefPubMed

129.

Draviam, V. M., Shapiro, I., Aldridge, B., & Sorger, P. K. (2006). Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells. The EMBO Journal, 25(12), 2814–2827. https://doi.org/10.1038/sj.emboj.7601168.CrossRefPubMedPubMedCentral

130.

Hadjihannas, M. V., Brückner, M., Jerchow, B., Birchmeier, W., Dietmaier, W., & Behrens, J. (2006). Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 103(28), 10747–10752. https://doi.org/10.1073/pnas.0604206103.CrossRefPubMedPubMedCentral

131.

Hadjihannas, M. V., Brückner, M., & Behrens, J. (2010). Conductin/axin2 and Wnt signalling regulates centrosome cohesion. EMBO Reports, 11(4), 317–324. https://doi.org/10.1038/embor.2010.23.CrossRefPubMedPubMedCentral

132.

Fumoto, K., Kadono, M., Izumi, N., & Kikuchi, A. (2009). Axin localizes to the centrosome and is involved in microtubule nucleation. EMBO Reports, 10(6), 606–613. https://doi.org/10.1038/embor.2009.45.CrossRefPubMedPubMedCentral

133.

Caldwell, C. M., Green, R. A., & Kaplan, K. B. (2007). APC mutations lead to cytokinetic failures in vitro and tetraploid genotypes in Min mice. The Journal of Cell Biology, 178(7), 1109–1120. https://doi.org/10.1083/jcb.200703186.CrossRefPubMedPubMedCentral

134.

Aoki, K., Aoki, M., Sugai, M., Harada, N., Miyoshi, H., Tsukamoto, T., et al. (2007). Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells. Oncogene, 26(24), 3511–3520. https://doi.org/10.1038/sj.onc.1210141.CrossRefPubMed

135.

Voloshanenko, O., Erdmann, G., Dubash, T. D., Augustin, I., Metzig, M., Moffa, G., et al. (2013). Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. Nature Communications, 4(1), 2610. https://doi.org/10.1038/ncomms3610.CrossRefPubMed

136.

Srinivas, U. S., Tan, B. W. Q., Vellayappan, B. A., & Jeyasekharan, A. D. (2019). ROS and the DNA damage response in cancer. Redox Biology, 25, 101084. https://doi.org/10.1016/j.redox.2018.101084.CrossRefPubMed

137.

Tichy, E. D., Pillai, R., Deng, L., Tischfield, J. A., Hexley, P., Babcock, G. F., & Stambrook, P. J. (2012). The abundance of Rad51 protein in mouse embryonic stem cells is regulated at multiple levels. Stem Cell Research, 9(2), 124–134. https://doi.org/10.1016/j.scr.2012.05.004.CrossRefPubMedPubMedCentral

138.

Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., et al. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature, 444(7120), 756–760. https://doi.org/10.1038/nature05236.CrossRefPubMed

139.

Gibson, B. A., & Kraus, W. L. (2012). New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nature Reviews. Molecular Cell Biology, 13(7), 411–424. https://doi.org/10.1038/nrm3376.CrossRefPubMed

140.

Eustermann, S., Videler, H., Yang, J.-C., Cole, P. T., Gruszka, D., Veprintsev, D., & Neuhaus, D. (2011). The DNA-binding domain of human PARP-1 interacts with DNA single-strand breaks as a monomer through its second zinc finger. Journal of Molecular Biology, 407(1), 149–170. https://doi.org/10.1016/j.jmb.2011.01.034.CrossRefPubMedPubMedCentral

141.

Armstrong, A. C., & Clay, V. (2019). Olaparib in germline-mutated metastatic breast cancer: implications of the OlympiAD trial. Future Oncology (London, England), 15(20), 2327–2335. https://doi.org/10.2217/fon-2018-0067.CrossRef

142.

Gelmon, K. A., Tischkowitz, M., Mackay, H., Swenerton, K., Robidoux, A., Tonkin, K., et al. (2011). Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. The Lancet Oncology, 12(9), 852–861. https://doi.org/10.1016/S1470-2045(11)70214-5.CrossRefPubMed

143.

Yamamoto, T. M., McMellen, A., Watson, Z. L., Aguilera, J., Ferguson, R., Nurmemmedov, E., et al. (2019). Activation of Wnt signaling promotes olaparib resistant ovarian cancer. Molecular Carcinogenesis, 68, 7. https://doi.org/10.1002/mc.23064.CrossRef

144.

Thorne, C. A., Hanson, A. J., Schneider, J., Tahinci, E., Orton, D., Cselenyi, C. S., et al. (2010). Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α. Nature Chemical Biology, 6(11), 829–836. https://doi.org/10.1038/nchembio.453.CrossRefPubMedPubMedCentral

145.

Li, B., Fei, D. L., Flaveny, C. A., Dahmane, N., Baubet, V., Wang, Z., et al. (2014). Pyrvinium attenuates Hedgehog signaling downstream of smoothened. Cancer Research, 74(17), 4811–4821. https://doi.org/10.1158/0008-5472.CAN-14-0317.CrossRefPubMedPubMedCentral

146.

Jun, S., Jung, Y.-S., Suh, H. N., Wang, W., Kim, M. J., Oh, Y. S., et al. (2016). LIG4 mediates Wnt signalling-induced radioresistance. Nature Communications, 7(1), 10994–10913. https://doi.org/10.1038/ncomms10994.CrossRefPubMedPubMedCentral

147.

Kanazawa, A., Tsukada, S., Sekine, A., Tsunoda, T., Takahashi, A., Kashiwagi, A., et al. (2004). Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes. American Journal of Human Genetics, 75(5), 832–843. https://doi.org/10.1086/425340.CrossRefPubMedPubMedCentral

148.

Zeve, D., Seo, J., Suh, J. M., Stenesen, D., Tang, W., Berglund, E. D., et al. (2012). Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. Cell Metabolism, 15(4), 492–504. https://doi.org/10.1016/j.cmet.2012.03.010.CrossRefPubMedPubMedCentral

149.

Mori, H., Prestwich, T. C., Reid, M. A., Longo, K. A., Gerin, I., Cawthorn, W. P., et al. (2012). Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition. The Journal of Clinical Investigation, 122(7), 2405–2416. https://doi.org/10.1172/JCI63604.CrossRefPubMedPubMedCentral

150.

Behari, J., Li, H., Liu, S., Stefanovic-Racic, M., Alonso, L., O'Donnell, C. P., et al. (2014). β-catenin links hepatic metabolic zonation with lipid metabolism and diet-induced obesity in mice. The American Journal of Pathology, 184(12), 3284–3298. https://doi.org/10.1016/j.ajpath.2014.08.022.CrossRefPubMedPubMedCentral

151.

Sethi, J. K., & Vidal-Puig, A. (2010). Wnt signalling and the control of cellular metabolism. The Biochemical Journal, 427(1), 1–17. https://doi.org/10.1042/BJ20091866.CrossRefPubMed

152.

Liberti, M. V., & Locasale, J. W. (2016). The Warburg effect: how does it benefit cancer cells? Trends in Biochemical Sciences, 41(3), 211–218. https://doi.org/10.1016/j.tibs.2015.12.001.CrossRefPubMedPubMedCentral

153.

Sherwood, V. (2015). WNT signaling: an emerging mediator of cancer cell metabolism? Molecular and Cellular Biology, 35(1), 2–10. https://doi.org/10.1128/MCB.00992-14.CrossRefPubMed

154.

Chafey, P., Finzi, L., Boisgard, R., Caüzac, M., Clary, G., Broussard, C., et al. (2009). Proteomic analysis of beta-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway. Proteomics, 9(15), 3889–3900. https://doi.org/10.1002/pmic.200800609.CrossRefPubMed

155.

Pate, K. T., Stringari, C., Sprowl-Tanio, S., Wang, K., TeSlaa, T., Hoverter, N. P., et al. (2014). Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. The EMBO Journal, 33(13), 1454–1473. https://doi.org/10.15252/embj.201488598.CrossRefPubMedPubMedCentral

156.

Lee, S. Y., Jeon, H. M., Ju, M. K., Kim, C. H., Yoon, G., Han, S. I., et al. (2012). Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism. Cancer Research, 72(14), 3607–3617. https://doi.org/10.1158/0008-5472.CAN-12-0006.CrossRefPubMed

157.

Dang, C. V., Le, A., & Gao, P. (2009). MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15(21), 6479–6483. https://doi.org/10.1158/1078-0432.CCR-09-0889.CrossRef

158.

Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867. https://doi.org/10.1038/nature01322.CrossRefPubMedPubMedCentral

159.

Crusz, S. M., & Balkwill, F. R. (2015). Inflammation and cancer: advances and new agents. Nature Reviews. Clinical Oncology, 12(10), 584–596. https://doi.org/10.1038/nrclinonc.2015.105.CrossRefPubMed

160.

Yeo, E.-J., Cassetta, L., Qian, B.-Z., Lewkowich, I., Li, J.-F., Stefater, J. A., et al. (2014). Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Research, 74(11), 2962–2973. https://doi.org/10.1158/0008-5472.CAN-13-2421.CrossRefPubMedPubMedCentral

161.

Ojalvo, L. S., Whittaker, C. A., Condeelis, J. S., & Pollard, J. W. (2010). Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. The Journal of Immunology, 184(2), 702–712. https://doi.org/10.4049/jimmunol.0902360.CrossRefPubMed

162.

Oguma, K., Oshima, H., Aoki, M., Uchio, R., Naka, K., Nakamura, S., et al. (2008). Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. The EMBO Journal, 27(12), 1671–1681. https://doi.org/10.1038/emboj.2008.105.CrossRefPubMedPubMedCentral

163.

Pukrop, T., Klemm, F., Hagemann, T., Gradl, D., Schulz, M., Siemes, S., et al. (2006). Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proceedings of the National Academy of Sciences of the United States of America, 103(14), 5454–5459. https://doi.org/10.1073/pnas.0509703103.CrossRefPubMedPubMedCentral

164.

Linde, N., Casanova-Acebes, M., Sosa, M. S., Mortha, A., Rahman, A., Farias, E., et al. (2018). Macrophages orchestrate breast cancer early dissemination and metastasis. Nature Communications, 9(1), 21. https://doi.org/10.1038/s41467-017-02481-5.CrossRefPubMedPubMedCentral

165.

Manicassamy, S., Reizis, B., Ravindran, R., Nakaya, H., Salazar-Gonzalez, R. M., Wang, Y.-C., & Pulendran, B. (2010). Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science, 329(5993), 849–853. https://doi.org/10.1126/science.1188510.CrossRefPubMedPubMedCentral

166.

Oderup, C., LaJevic, M., & Butcher, E. C. (2013). Canonical and noncanonical Wnt proteins program dendritic cell responses for tolerance. The Journal of Immunology, 190(12), 6126–6134. https://doi.org/10.4049/jimmunol.1203002.CrossRefPubMed

167.

Hong, Y., Manoharan, I., Suryawanshi, A., Shanmugam, A., Swafford, D., Ahmad, S., et al. (2016). Deletion of LRP5 and LRP6 in dendritic cells enhances antitumor immunity. Oncoimmunology, 5(4), e1115941. https://doi.org/10.1080/2162402X.2015.1115941.CrossRefPubMed

168.

Spranger, S., Bao, R., & Gajewski, T. F. (2015). Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature, 523(7559), 231–235. https://doi.org/10.1038/nature14404.CrossRefPubMed

169.

Luke, J. J., Bao, R., Sweis, R. F., Spranger, S., & Gajewski, T. F. (2019). WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, clincanres.1942.2018. https://doi.org/10.1158/1078-0432.CCR-18-1942.

170.

Holtzhausen, A., Zhao, F., Evans, K. S., Tsutsui, M., Orabona, C., Tyler, D. S., & Hanks, B. A. (2015). Melanoma-derived Wnt5a promotes local dendritic-cell expression of IDO and immunotolerance: opportunities for pharmacologic enhancement of immunotherapy. Cancer Immunology Research, 3(9), 1082–1095. https://doi.org/10.1158/2326-6066.CIR-14-0167.CrossRefPubMedPubMedCentral

171.

Fallarino, F., Grohmann, U., You, S., McGrath, B. C., Cavener, D. R., Vacca, C., et al. (2006). The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. The Journal of Immunology, 176(11), 6752–6761. https://doi.org/10.4049/jimmunol.176.11.6752.CrossRefPubMed

172.

Zhao, F., Xiao, C., Evans, K. S., Theivanthiran, T., DeVito, N., Holtzhausen, A., et al. (2018). Paracrine Wnt5a-β-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity, 48(1), 147–160.e7. https://doi.org/10.1016/j.immuni.2017.12.004.CrossRefPubMedPubMedCentral

173.

Khazaie, K., Blatner, N. R., Khan, M. W., Gounari, F., Gounaris, E., Dennis, K., et al. (2011). The significant role of mast cells in cancer. Cancer Metastasis Reviews, 30(1), 45–60. https://doi.org/10.1007/s10555-011-9286-z.CrossRefPubMed

174.

Yamaguchi, T., Nishijima, M., Tashiro, K., & Kawabata, K. (2016). Wnt-β-catenin signaling promotes the maturation of mast cells. BioMed Research International, 2016(7, article 1378), 2048987–2048988. https://doi.org/10.1155/2016/2048987.CrossRefPubMedPubMedCentral

175.

Tebroke, J., Lieverse, J. E., Säfholm, J., Schulte, G., Nilsson, G., & Rönnberg, E. (2019). Wnt-3a induces cytokine release in human mast cells. Cells, 8(11), 1372. https://doi.org/10.3390/cells8111372.CrossRefPubMedCentral

176.

Strouch, M. J., Cheon, E. C., Salabat, M. R., Krantz, S. B., Gounaris, E., Melstrom, L. G., et al. (2010). Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 16(8), 2257–2265. https://doi.org/10.1158/1078-0432.CCR-09-1230.CrossRef

177.

Jensen, H. K., Donskov, F., Marcussen, N., Nordsmark, M., Lundbeck, F., & von der Maase, H. (2009). Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 27(28), 4709–4717. https://doi.org/10.1200/JCO.2008.18.9498.CrossRef

178.

Trellakis, S., Bruderek, K., Dumitru, C. A., Gholaman, H., Gu, X., Bankfalvi, A., et al. (2011). Polymorphonuclear granulocytes in human head and neck cancer: enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease. International Journal of Cancer, 129(9), 2183–2193. https://doi.org/10.1002/ijc.25892.CrossRefPubMed

179.

Galdiero, M. R., Bianchi, P., Grizzi, F., Di Caro, G., Basso, G., Ponzetta, A., et al. (2016). Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer. International Journal of Cancer, 139(2), 446–456. https://doi.org/10.1002/ijc.30076.CrossRefPubMed

180.

Caruso, R. A., Bellocco, R., Pagano, M., Bertoli, G., Rigoli, L., & Inferrera, C. (2002). Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 15(8), 831–837. https://doi.org/10.1097/01.MP.0000020391.98998.6B.CrossRef

181.

Chao, T., Furth, E. E., & Vonderheide, R. H. (2016). CXCR2-dependent accumulation of tumor-associated neutrophils regulates T-cell immunity in pancreatic ductal adenocarcinoma. Cancer Immunology Research, 4(11), 968–982. https://doi.org/10.1158/2326-6066.CIR-16-0188.CrossRefPubMedPubMedCentral

182.

Skokowa, J., Cario, G., Uenalan, M., Schambach, A., Germeshausen, M., Battmer, K., et al. (2006). LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. Nature Medicine, 12(10), 1191–1197. https://doi.org/10.1038/nm1474.CrossRefPubMed

183.

Verbeek, S., Izon, D., Hofhuis, F., Robanus-Maandag, E., te Riele, H., van de Wetering, M., et al. (1995). An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature, 374(6517), 70–74. https://doi.org/10.1038/374070a0.CrossRefPubMed

184.

Staal, F. J., Meeldijk, J., Moerer, P., Jay, P., van de Weerdt, B. C., Vainio, S., et al. (2001). Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. European Journal of Immunology, 31(1), 285–293. https://doi.org/10.1002/1521-4141(200101)31:1<285::AID-IMMU285>3.0.CO;2-D.CrossRefPubMed

185.

Wang, B., Tian, T., Kalland, K.-H., Ke, X., & Qu, Y. (2018). Targeting Wnt/β-catenin signaling for cancer immunotherapy. Trends in Pharmacological Sciences, 39(7), 648–658. https://doi.org/10.1016/j.tips.2018.03.008.CrossRefPubMed

186.

Wong, C., Chen, C., Wu, Q., Liu, Y., & Zheng, P. (2015). A critical role for the regulated wnt-myc pathway in naive T cell survival. The Journal of Immunology, 194(1), 158–167. https://doi.org/10.4049/jimmunol.1401238.CrossRefPubMed

187.

Yu, Q., Sharma, A., Oh, S. Y., Moon, H.-G., Hossain, M. Z., Salay, T. M., et al. (2009). T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nature Immunology, 10(9), 992–999. https://doi.org/10.1038/ni.1762.CrossRefPubMedPubMedCentral

188.

Notani, D., Gottimukkala, K. P., Jayani, R. S., Limaye, A. S., Damle, M. V., Mehta, S., et al. (2010). Global regulator SATB1 recruits beta-catenin and regulates T(H)2 differentiation in Wnt-dependent manner. PLoS Biology, 8(1), e1000296. https://doi.org/10.1371/journal.pbio.1000296.CrossRefPubMedPubMedCentral

189.

Dai, W., Liu, F., Li, C., Lu, Y., Lu, X., Du, S., et al. (2016). Blockade of Wnt/β-catenin pathway aggravated silica-induced lung inflammation through Tregs regulation on Th immune responses. Mediators of Inflammation, 2016(6), 6235614–6235614. https://doi.org/10.1155/2016/6235614.CrossRefPubMedPubMedCentral

190.

Ding, Y., Shen, S., Lino, A. C., Curotto de Lafaille, M. A., & Lafaille, J. J. (2008). Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells. Nature Medicine, 14(2), 162–169. https://doi.org/10.1038/nm1707.CrossRefPubMed

191.

Sun, X., Liu, S., Wang, D., Zhang, Y., Li, W., Guo, Y., et al. (2017). Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling. Oncotarget, 8(9), 15168–15181. https://doi.org/10.18632/oncotarget.14834.CrossRefPubMedPubMedCentral

192.

Keerthivasan, S., Aghajani, K., Dose, M., Molinero, L., Khan, M. W., Venkateswaran, V., et al. (2014). β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells. Science Translational Medicine, 6(225), 225ra28–225ra28. https://doi.org/10.1126/scitranslmed.3007607.CrossRef

193.

Trujillo, J. A., Sweis, R. F., Bao, R., & Luke, J. J. (2018). T cell-inflamed versus non-T cell-inflamed tumors: a conceptual framework for cancer immunotherapy drug development and combination therapy selection. Cancer Immunology Research, 6(9), 990–1000. https://doi.org/10.1158/2326-6066.CIR-18-0277.CrossRefPubMedPubMedCentral

194.

Spranger, S., & Gajewski, T. F. (2018). Impact of oncogenic pathways on evasion of antitumour immune responses. Nature Reviews. Cancer, 18(3), 139–147. https://doi.org/10.1038/nrc.2017.117.CrossRefPubMedPubMedCentral

195.

Sweis, R. F., Spranger, S., Bao, R., Paner, G. P., Stadler, W. M., Steinberg, G., & Gajewski, T. F. (2016). Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer. Cancer Immunology Research, 4(7), 563–568. https://doi.org/10.1158/2326-6066.CIR-15-0274.CrossRefPubMedPubMedCentral

196.

Murata, Y., Saito, Y., Kotani, T., & Matozaki, T. (2018). CD47-signal regulatory protein α signaling system and its application to cancer immunotherapy. Cancer Science, 109(8), 2349–2357. https://doi.org/10.1111/cas.13663.CrossRefPubMedPubMedCentral

197.

Gowda, P., Patrick, S., Singh, A., Sheikh, T., & Sen, E. (2018). Mutant isocitrate dehydrogenase 1 disrupts PKM2-β-catenin-BRG1 transcriptional network-driven CD47 expression. Molecular and Cellular Biology, 38(9), 597. https://doi.org/10.1128/MCB.00001-18.CrossRef

198.

Buchbinder, E. I., & Desai, A. (2016). CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. American Journal of Clinical Oncology, 39(1), 98–106. https://doi.org/10.1097/COC.0000000000000239.CrossRefPubMedPubMedCentral

199.

Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., et al. (2017). T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science, 355(6332), 1428–1433. https://doi.org/10.1126/science.aaf1292.CrossRefPubMedPubMedCentral

200.

Yokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M., & Saito, T. (2012). Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. The Journal of Experimental Medicine, 209(6), 1201–1217. https://doi.org/10.1084/jem.20112741.CrossRefPubMedPubMedCentral

201.

Chovanec, M., Cierna, Z., Miskovska, V., Machalekova, K., Kalavska, K., Rejlekova, K., et al. (2018). βcatenin is a marker of poor clinical characteristics and suppressed immune infiltration in testicular germ cell tumors. BMC Cancer, 18(1), 1062–1010. https://doi.org/10.1186/s12885-018-4929-x.CrossRefPubMedPubMedCentral

202.

Castagnoli, L., Cancila, V., Cordoba-Romero, S. L., Faraci, S., Talarico, G., Belmonte, B., et al. (2019). WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer. Oncogene, 38(21), 4047–4060. https://doi.org/10.1038/s41388-019-0700-2.CrossRefPubMedPubMedCentral

203.

Casey, S. C., Tong, L., Li, Y., Do, R., Walz, S., Fitzgerald, K. N., et al. (2016). MYC regulates the antitumor immune response through CD47 and PD-L1. Science, 352(6282), 227–231. https://doi.org/10.1126/science.aac9935.CrossRefPubMedPubMedCentral

204.

Kalbasi, A., & Ribas, A. (2020). Tumour-intrinsic resistance to immune checkpoint blockade. Nature Reviews. Immunology, 20(1), 25–39. https://doi.org/10.1038/s41577-019-0218-4.CrossRefPubMed

205.

Rotte, A. (2019). Combination of CTLA-4 and PD-1 blockers for treatment of cancer. Journal of Experimental and Clinical Cancer Research, 38(1), 255–212. https://doi.org/10.1186/s13046-019-1259-z.CrossRefPubMedPubMedCentral

206.

Shah, K. V., Chien, A. J., Yee, C., & Moon, R. T. (2008). CTLA-4 is a direct target of Wnt/beta-catenin signaling and is expressed in human melanoma tumors. The Journal of Investigative Dermatology, 128(12), 2870–2879. https://doi.org/10.1038/jid.2008.170.CrossRefPubMedPubMedCentral

207.

Blando, J., Sharma, A., Higa, M. G., Zhao, H., Vence, L., Yadav, S. S., et al. (2019). Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America, 116(5), 1692–1697. https://doi.org/10.1073/pnas.1811067116.CrossRefPubMedPubMedCentral

208.

Guo, Y., Xiao, L., Sun, L., & Liu, F. (2012). Wnt/beta-catenin signaling: a promising new target for fibrosis diseases. Physiological Research, 61(4), 337–346.CrossRefPubMed

209.

Madan, B., Patel, M. B., Zhang, J., Bunte, R. M., Rudemiller, N. P., Griffiths, R., et al. (2016). Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis. Kidney International. https://doi.org/10.1016/j.kint.2016.01.017.

210.

Madan, B., & Virshup, D. M. (2015). Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs. Molecular Cancer Therapeutics, 14(5), 1087–1094. https://doi.org/10.1158/1535-7163.MCT-14-1038.CrossRefPubMed

Springer Medizin

Wnts and the hallmarks of cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

Brain tumor vessels—a barrier for drug delivery

Regulation of breast cancer metastasis signaling by miRNAs

RNA-biology ruling cancer progression? Focus on 3′UTRs and splicing

CDK7 inhibitors as anticancer drugs