nach oben

Breast Cancer

Erschienen in:

01.04.2012 | Special Feature

The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis

verfasst von: Takeshi Imamura, Atsuhiko Hikita, Yasumichi Inoue

Erschienen in: Breast Cancer | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

Transforming growth factor-β (TGF-β) ligand is a multifunctional growth factor that regulates various cell behavior, such as cell proliferation, differentiation, migration, and apoptosis. Because TGF-β is a potent growth inhibitor, abnormalities in TGF-β signaling result in carcinogenesis. In addition to tumor suppressor function, TGF-β acts as an oncogenic factor. In particular, TGF-β signaling plays an important role during metastasis of breast cancer. Recently, epithelial-mesenchymal transition (EMT) has been shown to confer malignant properties such as cell motility and invasiveness to cancer cells and plays crucial roles during cancer metastasis. Moreover, breast stem-like cells exhibit EMT properties. Because TGF-β is a potent regulator of EMT as well as cell stemness, TGF-β signaling might play a crucial role in the regulation of breast cancer stem cells.

Feng XH, Derynck R. Specificity and versatility in tgf-β signaling through Smads. Annu Rev Cell Dev Biol. 2005;21:659–93.PubMedCrossRef

Wakefield LM, Roberts AB. TGF-β signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev. 2002;12:22–9.PubMedCrossRef

Bierie B, Moses HL. TGFβ: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 2006;6:506–20.PubMedCrossRef

Ikushima H, Miyazono K. TGFβ signalling: a complex web in cancer progression. Nat Rev Cancer. 2010;10:415–24.PubMedCrossRef

Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordón-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3:537–49.PubMedCrossRef

Katsuno Y, Hanyu A, Kanda H, Ishikawa Y, Akiyama F, Iwase T, et al. Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene. 2008;27:6322–33.PubMedCrossRef

Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, et al. TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008;133:66–77.PubMedCrossRef

Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, et al. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest. 1996;98:1544–9.PubMedCrossRef

Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, et al. TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 1999;103:197–206.PubMedCrossRef

10.

Heldin CH, Miyazono K, ten Dijke P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390:465–71.PubMedCrossRef

11.

Inoue Y, Imamura T. Regulation of TGF-β family signaling by E3 ubiquitin ligases. Cancer Sci. 2008;99:2107–12.PubMedCrossRef

12.

Ikushima H, Miyazono K. Cellular context-dependent “colors” of transforming growth factor-beta signaling. Cancer Sci. 2010;101:306–12.PubMedCrossRef

13.

Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-β superfamily signalling. Genes Cells. 2002;7:1191–204.PubMedCrossRef

14.

Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, et al. The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. Cell. 1997;89:1165–73.PubMedCrossRef

15.

Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, et al. Smad6 inhibits signalling by the TGF-β superfamily. Nature. 1997;389:622–66.PubMedCrossRef

16.

Takase M, Imamura T, Sampath TK, Takeda K, Ichijo H, Miyazono K, et al. Induction of Smad6 mRNA by bone morphogenetic proteins. Biochem Biophys Res Commun. 1998;244:26–9.PubMedCrossRef

17.

Hanyu A, Ishidou Y, Ebisawa T, Shimanuki T, Imamura T, Miyazono K. The N domain of Smad7 is essential for specific inhibition of transforming growth factor-β signaling. J Cell Biol. 2001;155:1017–27.PubMedCrossRef

18.

Seoane J, Le HV, Shen L, Anderson SA, Massagué J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 2004;117:211–23.PubMedCrossRef

19.

Gomis RR, Alarcón C, Nadal C, Van Poznak C, Massagué J. C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells. Cancer Cell. 2006;10:203–14.PubMedCrossRef

20.

Feng XH, Lin X, Derynck R. Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15(Ink4B) transcription in response to TGF-β. EMBO J. 2000;19:5178–93.PubMedCrossRef

21.

Pardali K, Kurisaki A, Morén A, ten Dijke P, Kardassis D, Moustakas A. Role of Smad proteins and transcription factor Sp1 in p21^Waf1/Cip1 regulation by transforming growth factor-β. J Biol Chem. 2000;275:29244–56.PubMedCrossRef

22.

Koinuma D, Tsutsumi S, Kamimura N, Taniguchi H, Miyazawa K, Sunamura M, et al. ChIP-chip analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in TGF-β signaling. Mol Cell Biol. 2009;29:172–86.PubMedCrossRef

23.

Chen CR, Kang Y, Siegel PM, Massagué J. E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression. Cell. 2002;110:19–32.PubMedCrossRef

24.

Yagi K, Furuhashi M, Aoki H, Goto D, Kuwano H, Sugamura K, et al. c-myc is a downstream target of the Smad pathway. J Biol Chem. 2002;277:854–61.PubMedCrossRef

25.

Seoane J, Le H-V, Massagué J. Myc suppression of the p21^Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 2002;419:729–34.PubMedCrossRef

26.

Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, et al. Repression of p15^INK4b expression by Myc through association with Miz-1. Nat Cell Biol. 2001;3:392–9.PubMedCrossRef

27.

Seoane J, Pouponnot C, Staller P, Schader M, Eilers M, Massagué J. TGFβ influences Myc, Miz-1 and Smad to control the CDK inhibitor p15^INK4b. Nat Cell Biol. 2001;3:400–8.PubMedCrossRef

28.

Perk J, Iavarone A, Benezra R. Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer. 2005;5:603–14.PubMedCrossRef

29.

Kang Y, Chen CR, Massagué J. A self-enabling TGFβ response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. Mol Cell. 2003;11:915–26.PubMedCrossRef

30.

Valderrama-Carvajal H, Cocolakis E, Lacerte A, Lee EH, Krystal G, Ali S, et al. Activin/TGF-β induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP. Nat Cell Biol. 2002;4:963–9.PubMedCrossRef

31.

Ribeiro A, Bronk SF, Roberts PJ, Urrutia R, Gores GJ. The transforming growth factor β₁-inducible transcription factor TIEG1, mediates apoptosis through oxidative stress. Hepatology. 1999;30:1490–7.PubMedCrossRef

32.

Wildey GM, Patil S, Howe PH. Smad3 potentiates transforming growth factor β (TGFβ)-induced apoptosis and expression of the BH3-only protein Bim in WEHI 231 B lymphocytes. J Biol Chem. 2003;278:18069–77.PubMedCrossRef

33.

Jang CW, Chen CH, Chen CC, Chen JY, Su YH, Chen RH. TGF-β induces apoptosis through Smad-mediated expression of DAP-kinase. Nat Cell Biol. 2002;4:51–8.PubMedCrossRef

34.

Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet. 2001;28:184–7.PubMedCrossRef

35.

Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271:350–3.PubMedCrossRef

36.

Liang M, Liang YY, Wrighton K, Ungermannova D, Wang XP, Brunicardi FC, et al. Ubiquitination and proteolysis of cancer-derived Smad4 mutants by SCFSkp2. Mol Cell Biol. 2004;24:7524–37.PubMedCrossRef

37.

Deheuninck J, Luo K. Ski and SnoN, poent negative regulators of TGF-β signaling. Cell Res. 2009;19:47–57.PubMedCrossRef

38.

Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CS. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Mol Cell Biol. 2007;27:6068–83.PubMedCrossRef

39.

Kurokawa M, Mitani K, Imai Y, Ogawa S, Yazaki Y, Hirai H. The t(3;21) fusion product, AML/Evi-1, interacts with Smad3 and blocks transforming growth factor-β-mediated growth inhibition of myeloid cells. Blood. 1998;92:4003–12.PubMed

40.

Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.PubMedCrossRef

41.

Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.PubMedCrossRef

42.

Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98:1512–20.PubMedCrossRef

43.

Xu J, Lamouille S, Derynck R. TGF-β-induced epithelial to mesenchymal transition. Cell Res. 2009;19:156–72.PubMedCrossRef

44.

Hurd TW, Gao L, Roh MH, Macara IG, Margolis B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol. 2003;5:137–42.PubMedCrossRef

45.

Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL. Regulation of the polarity protein Par6 by TGFβ receptors controls epithelial cell plasticity. Science. 2005;307:1603–9.PubMedCrossRef

46.

Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996;10:2462–77.PubMedCrossRef

47.

Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, Downward J, et al. Ras and TGFβ cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol. 2002;156:299–313.PubMedCrossRef

48.

Vogelmann R, Nguyen-Tat MD, Giehl K, Adler G, Wedlich D, Menke A. TGFβ-induced downregulation of E-cadherin-based cell–cell adhesion depends on PI3-kinase and PTEN. J Cell Sci. 2005;118:4901–12.PubMedCrossRef

49.

Horiguchi K, Shirakihara T, Nakano A, Imamura T, Miyazono K, Saitoh M. Role of Ras signaling in the induction of Snail by transforming growth factor-β. J Biol Chem. 2009;284:245–53.PubMedCrossRef

50.

Araki S, Eitel JA, Batuello CN, Bijangi-Vishehsaraei K, Xie XJ, Danielpour D, et al. TGF-β1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J Clin Invest. 2010;120:290–302.PubMedCrossRef

51.

Kondo H, Guo J, Bringhurst FR. Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res. 2002;17:1667–79.PubMedCrossRef

52.

Bandyopadhyay A, Agyin JK, Wang L, Tang Y, Lei X, Story BM, et al. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-β type I receptor kinase inhibitor. Cancer Res. 2006;66:6714–21.PubMedCrossRef

53.

Ge R, Rajeev V, Ray P, Lattime E, Rittling S, Medicherla S, et al. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-β type I receptor kinase in vivo. Clin Cancer Res. 2006;12:4315–30.PubMedCrossRef

54.

Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, et al. Ki26894, a novel transforming growth factor-β type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Sci. 2007;98:127–33.PubMedCrossRef

55.

Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRef

56.

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMedCrossRef

57.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.PubMedCrossRef

58.

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedCrossRef

59.

Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–9.PubMedCrossRef

Titel: The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis
verfasst von: Takeshi Imamura
Atsuhiko Hikita
Yasumichi Inoue
Publikationsdatum: 01.04.2012
Verlag: Springer Japan
Erschienen in: Breast Cancer / Ausgabe 2/2012
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-011-0321-2

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis

Abstract

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 2/2012

Educational program and testing using images for the standardization of breast cancer screening by ultrasonography

Should we treat minimal breast cancer lesions?

Possible available treatment option for early stage, small, node-negative, and HER2-overexpressing breast cancer

Ultrasonography- and/or mammography-guided breast conserving surgery for ductal carcinoma in situ of the breast: experience with 87 lesions

Paradigm shift in axilla surgery for breast cancer patients treated with sentinel node biopsy

Nodular fasciitis of the breast

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie