Skip to main content
Erschienen in:

08.05.2020 | Original paper

The hedgehog pathway regulates cancer stem cells in serous adenocarcinoma of the ovary

verfasst von: Smarakan Sneha, Rohit P. Nagare, Chirukandath Sidhanth, Syama Krishnapriya, Manoj Garg, Balaji Ramachandran, Kanchan Murhekar, Shirley Sundersingh, Trivadi S. Ganesan

Erschienen in: Cellular Oncology | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Signaling by cancer stem cells (CSCs) is known to occur at least in part through conserved developmental pathways. Here, the role of one of these pathways, i.e., the hedgehog pathway, was evaluated in high-grade serous ovarian carcinoma (HGSOC).

Methods and results

We found that in HGSOC, hedgehog inhibitors (HHIs) GANT61, LDE225 and GDC0449 reduced or inhibited the formation of spheroids enriched in CSCs. Primary malignant cells (PMCs) in ascites from HGSOC patients cultured in the presence of HHIs showed significant reduction in CSCs. Sonic hedgehog (SHH) significantly increased the expression of ALDH1A1, which was inhibited by GANT61. In the presence of a SHH neutralizing antibody (5E1), a significant reduction in the number of spheroids was observed in HGSOC-derived cell lines. Further, the motility, migration and clonogenic growth of the cells were significantly reduced by HHIs. In the presence of GANT61, a reduction of cells from PMCs in the G0 phase of the cell cycle was observed. The magnitude of difference in expression of Gli1 in tumors from the same HGSOC patients at presentation and at interval debulking surgery was greater in patients who had a recurrence on follow up. GANT61 also significantly inhibited the growth of CSCs in nude mice. Finally, RNA sequencing of HGSOC cells treated with GANT61 showed a significantly reduced expression of CSC markers.

Conclusions

Our results indicate that the hedgehog pathway plays an important role in maintaining the integrity of CSCs in HGSOC and could be a potential therapeutic target.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat A. Desai, Y. Yan, S.L. Gerson, Concise reviews: cancer stem cell targeted therapies: toward clinical success. Stem Cells Transl. Med. 8, 75–81 (2019)CrossRef A. Desai, Y. Yan, S.L. Gerson, Concise reviews: cancer stem cell targeted therapies: toward clinical success. Stem Cells Transl. Med. 8, 75–81 (2019)CrossRef
2.
Zurück zum Zitat R.P. Nagare, S. Sneha, S.K. Priya, T.S. Ganesan, Cancer stem cells - are surface markers alone sufficient? Curr. Stem Cell Res. Ther. 12, 37–44 (2017)CrossRef R.P. Nagare, S. Sneha, S.K. Priya, T.S. Ganesan, Cancer stem cells - are surface markers alone sufficient? Curr. Stem Cell Res. Ther. 12, 37–44 (2017)CrossRef
3.
Zurück zum Zitat N. Perrimon, C. Pitsouli, B.Z. Shilo, Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb. Perspect. Biol. 4, a005975 (2012)CrossRef N. Perrimon, C. Pitsouli, B.Z. Shilo, Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb. Perspect. Biol. 4, a005975 (2012)CrossRef
4.
Zurück zum Zitat S. Schmid, M. Bieber, F. Zhang, M. Zhang, B. He, D. Jablons, N.N. Teng, Wnt and hedgehog gene pathway expression in serous ovarian cancer. Int. J. Gynecol. Cancer 21, 975–980 (2011)CrossRef S. Schmid, M. Bieber, F. Zhang, M. Zhang, B. He, D. Jablons, N.N. Teng, Wnt and hedgehog gene pathway expression in serous ovarian cancer. Int. J. Gynecol. Cancer 21, 975–980 (2011)CrossRef
5.
Zurück zum Zitat X. Liao, M.K. Siu, C.W. Au, E.S. Wong, H.Y. Chan, P.P. Ip, H.Y. Ngan, A.N. Cheung, Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30, 131–140 (2009)CrossRef X. Liao, M.K. Siu, C.W. Au, E.S. Wong, H.Y. Chan, P.P. Ip, H.Y. Ngan, A.N. Cheung, Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30, 131–140 (2009)CrossRef
6.
Zurück zum Zitat A.D. Steg, A.A. Katre, K.S. Bevis, A. Ziebarth, Z.C. Dobbin, M.M. Shah, R.D. Alvarez, C.N. Landen, Smoothened antagonists reverse taxane resistance in ovarian cancer. Mol. Cancer Ther. 11, 1587–1597 (2012)CrossRef A.D. Steg, A.A. Katre, K.S. Bevis, A. Ziebarth, Z.C. Dobbin, M.M. Shah, R.D. Alvarez, C.N. Landen, Smoothened antagonists reverse taxane resistance in ovarian cancer. Mol. Cancer Ther. 11, 1587–1597 (2012)CrossRef
7.
Zurück zum Zitat F.D. Ibrahim, Preliminary studies on the physiological and pharmacological actions of the extract of Orobanche crenata. J. Egypt. Med. Assoc. 51, 939–948 (1968)PubMed F.D. Ibrahim, Preliminary studies on the physiological and pharmacological actions of the extract of Orobanche crenata. J. Egypt. Med. Assoc. 51, 939–948 (1968)PubMed
8.
Zurück zum Zitat D. Abetov, Z. Mustapova, T. Saliev, D. Bulanin, K. Batyrbekov, C.P. Gilman, Novel small molecule inhibitors of cancer stem cell signaling pathways. Stem Cell Rev. 11, 909–918 (2015)CrossRef D. Abetov, Z. Mustapova, T. Saliev, D. Bulanin, K. Batyrbekov, C.P. Gilman, Novel small molecule inhibitors of cancer stem cell signaling pathways. Stem Cell Rev. 11, 909–918 (2015)CrossRef
9.
Zurück zum Zitat T. Ishiguro, H. Ohata, A. Sato, K. Yamawaki, T. Enomoto, K. Okamoto, Tumor-derived spheroids: relevance to cancer stem cells and clinical applications. Cancer Sci. 108, 283–289 (2017)CrossRef T. Ishiguro, H. Ohata, A. Sato, K. Yamawaki, T. Enomoto, K. Okamoto, Tumor-derived spheroids: relevance to cancer stem cells and clinical applications. Cancer Sci. 108, 283–289 (2017)CrossRef
10.
Zurück zum Zitat P.A. Bignone, K.Y. Lee, Y. Liu, G. Emilion, J. Finch, A.E. Soosay, F.M. Charnock, S. Beck, I. Dunham, A.J. Mungall, T.S. Ganesan, RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. Oncogene 26, 683–700 (2007)CrossRef P.A. Bignone, K.Y. Lee, Y. Liu, G. Emilion, J. Finch, A.E. Soosay, F.M. Charnock, S. Beck, I. Dunham, A.J. Mungall, T.S. Ganesan, RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. Oncogene 26, 683–700 (2007)CrossRef
11.
Zurück zum Zitat R.C. Dregalla, J. Zhou, R.R. Idate, C.L. Battaglia, H.L. Liber, S.M. Bailey, Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany N. Y.) 2, 691–708 (2010) R.C. Dregalla, J. Zhou, R.R. Idate, C.L. Battaglia, H.L. Liber, S.M. Bailey, Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany N. Y.) 2, 691–708 (2010)
12.
Zurück zum Zitat S.J. Scales, F.J. de Sauvage, Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol. Sci. 30, 303–312 (2009)CrossRef S.J. Scales, F.J. de Sauvage, Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol. Sci. 30, 303–312 (2009)CrossRef
13.
Zurück zum Zitat N. Gopalakrishnan, N.D. Sivasithamparam, H. Devaraj, Synergistic association of Notch and NFkappaB signaling and role of Notch signaling in modulating epithelial to mesenchymal transition in colorectal adenocarcinoma. Biochimie 107 Pt B, 310–318 (2014)CrossRef N. Gopalakrishnan, N.D. Sivasithamparam, H. Devaraj, Synergistic association of Notch and NFkappaB signaling and role of Notch signaling in modulating epithelial to mesenchymal transition in colorectal adenocarcinoma. Biochimie 107 Pt B, 310–318 (2014)CrossRef
14.
Zurück zum Zitat M. Lauth, A. Bergstrom, T. Shimokawa, R. Toftgard, Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc. Natl. Acad. Sci. U. S. A. 104, 8455–8460 (2007) M. Lauth, A. Bergstrom, T. Shimokawa, R. Toftgard, Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc. Natl. Acad. Sci. U. S. A. 104, 8455–8460 (2007)
15.
Zurück zum Zitat S. Pan, X. Wu, J. Jiang, W. Gao, Y. Wan, D. Cheng, D. Han, J. Liu, N.P. Englund, Y. Wang, S. Peukert, K. Miller-Moslin, J. Yuan, R. Guo, M. Matsumoto, A. Vattay, Y. Jiang, J. Tsao, F. Sun, A.C. Pferdekamper, S. Dodd, Tuntland T, W. Maniara, J.F. Kelleher, Y.M. Yao, M. Warmuth, J. Williams, M. Dorsch, Discovery of NVP-LDE225, a potent and selective smoothened antagonist. ACS Med. Chem. Lett. 1, 130–134 (2010)CrossRef S. Pan, X. Wu, J. Jiang, W. Gao, Y. Wan, D. Cheng, D. Han, J. Liu, N.P. Englund, Y. Wang, S. Peukert, K. Miller-Moslin, J. Yuan, R. Guo, M. Matsumoto, A. Vattay, Y. Jiang, J. Tsao, F. Sun, A.C. Pferdekamper, S. Dodd, Tuntland T, W. Maniara, J.F. Kelleher, Y.M. Yao, M. Warmuth, J. Williams, M. Dorsch, Discovery of NVP-LDE225, a potent and selective smoothened antagonist. ACS Med. Chem. Lett. 1, 130–134 (2010)CrossRef
16.
Zurück zum Zitat P.B. Gupta, T.T. Onder, G. Jiang, K. Tao, C. Kuperwasser, R.A. Weinberg, E.S. Lander, Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138, 645–659 (2009)CrossRef P.B. Gupta, T.T. Onder, G. Jiang, K. Tao, C. Kuperwasser, R.A. Weinberg, E.S. Lander, Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138, 645–659 (2009)CrossRef
17.
Zurück zum Zitat B.A. Kaipparettu, I. Kuiatse, B. Tak-Yee Chan, M. Benny Kaipparettu, A.V. Lee, S. Oesterreich, Novel egg white-based 3-D cell culture system. Biotechniques 45, 165–168 (2008) 170 – 161CrossRef B.A. Kaipparettu, I. Kuiatse, B. Tak-Yee Chan, M. Benny Kaipparettu, A.V. Lee, S. Oesterreich, Novel egg white-based 3-D cell culture system. Biotechniques 45, 165–168 (2008) 170 – 161CrossRef
18.
Zurück zum Zitat Z. Darzynkiewicz, G. Juan, E. Bedner, Determining cell cycle stages by flow cytometry. Curr. Protoc. Cell Biol. 1, 8.4.1–8.4.18 (1999) Z. Darzynkiewicz, G. Juan, E. Bedner, Determining cell cycle stages by flow cytometry. Curr. Protoc. Cell Biol. 1, 8.4.1–8.4.18 (1999)
19.
Zurück zum Zitat R.P. Nagare, S. Sneha, S. Ramesh, T.S. Ganesan, Analysis of hematopoietic stem cells using a composite approach. Int. J. Biochem. Cell Biol. 109, 82–89 (2019)CrossRef R.P. Nagare, S. Sneha, S. Ramesh, T.S. Ganesan, Analysis of hematopoietic stem cells using a composite approach. Int. J. Biochem. Cell Biol. 109, 82–89 (2019)CrossRef
20.
Zurück zum Zitat Y.C. Wang, Y.T. Yo, H.Y. Lee, Y.P. Liao, T.K. Chao, P.H. Su, H.C. Lai, ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am. J. Pathol. 180, 1159–1169 (2012)CrossRef Y.C. Wang, Y.T. Yo, H.Y. Lee, Y.P. Liao, T.K. Chao, P.H. Su, H.C. Lai, ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am. J. Pathol. 180, 1159–1169 (2012)CrossRef
21.
Zurück zum Zitat S. Krishna Priya, K. Kumar, K.R. Hiran, M.R. Bindhu, R.P. Nagare, D.K. Vijaykumar, T.S. Ganesan, Expression of a novel endothelial marker, C-type lectin 14A, in epithelial ovarian cancer and its prognostic significance. Int. J. Clin. Oncol. 22, 107–117 (2017)CrossRef S. Krishna Priya, K. Kumar, K.R. Hiran, M.R. Bindhu, R.P. Nagare, D.K. Vijaykumar, T.S. Ganesan, Expression of a novel endothelial marker, C-type lectin 14A, in epithelial ovarian cancer and its prognostic significance. Int. J. Clin. Oncol. 22, 107–117 (2017)CrossRef
22.
Zurück zum Zitat S. Condello, C.A. Morgan, S. Nagdas, L. Cao, J. Turek, T.D. Hurley, and D. Matei, beta-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene 34, 2297–2308 (2015) S. Condello, C.A. Morgan, S. Nagdas, L. Cao, J. Turek, T.D. Hurley, and D. Matei, beta-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene 34, 2297–2308 (2015)
23.
Zurück zum Zitat S. Sneha, R.P. Nagare, P. Manasa, S. Vasudevan, A. Shabna, T.S. Ganesan, Analysis of human stem cell transcription factors. Cell. Reprogram. 21, 171–180 (2019) S. Sneha, R.P. Nagare, P. Manasa, S. Vasudevan, A. Shabna, T.S. Ganesan, Analysis of human stem cell transcription factors. Cell. Reprogram. 21, 171–180 (2019)
24.
Zurück zum Zitat H.G. Lee, S.J. Shin, H.W. Chung, S.H. Kwon, S.D. Cha, J.E. Lee, C.H. Cho, Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell. J. Gynecol. Oncol. 28, e14 (2017) H.G. Lee, S.J. Shin, H.W. Chung, S.H. Kwon, S.D. Cha, J.E. Lee, C.H. Cho, Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell. J. Gynecol. Oncol. 28, e14 (2017)
25.
Zurück zum Zitat H.R. Maun, X. Wen, A. Lingel, F.J. de Sauvage, R.A. Lazarus, S.J. Scales, S.G. Hymowitz, Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site. J. Biol. Chem. 285, 26570–26580 (2010)CrossRef H.R. Maun, X. Wen, A. Lingel, F.J. de Sauvage, R.A. Lazarus, S.J. Scales, S.G. Hymowitz, Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site. J. Biol. Chem. 285, 26570–26580 (2010)CrossRef
26.
Zurück zum Zitat O.H. Yilmaz, R. Valdez, B.K. Theisen, W. Guo, D.O. Ferguson, H. Wu, S.J. Morrison, Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475–482 (2006)CrossRef O.H. Yilmaz, R. Valdez, B.K. Theisen, W. Guo, D.O. Ferguson, H. Wu, S.J. Morrison, Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475–482 (2006)CrossRef
27.
Zurück zum Zitat M.C. Boelens, T.J. Wu, B.Y. Nabet, B. Xu, Y. Qiu, T. Yoon, D.J. Azzam, C. Twyman-Saint, B.Z. Victor, H. Wiemann, P.J. Ishwaran, J. Ter Brugge, J. Jonkers, Slingerland, A.J. Minn, Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 159, 499–513 (2014)CrossRef M.C. Boelens, T.J. Wu, B.Y. Nabet, B. Xu, Y. Qiu, T. Yoon, D.J. Azzam, C. Twyman-Saint, B.Z. Victor, H. Wiemann, P.J. Ishwaran, J. Ter Brugge, J. Jonkers, Slingerland, A.J. Minn, Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 159, 499–513 (2014)CrossRef
28.
Zurück zum Zitat L. Hernandez, M.K. Kim, L.T. Lyle, K.P. Bunch, C.D. House, F. Ning, A.M. Noonan, C.M. Annunziata, Characterization of ovarian cancer cell lines as in vivo models for preclinical studies. Gynecol. Oncol. 142, 332–340 (2016)CrossRef L. Hernandez, M.K. Kim, L.T. Lyle, K.P. Bunch, C.D. House, F. Ning, A.M. Noonan, C.M. Annunziata, Characterization of ovarian cancer cell lines as in vivo models for preclinical studies. Gynecol. Oncol. 142, 332–340 (2016)CrossRef
29.
Zurück zum Zitat A.K. Mitra, D.A. Davis, S. Tomar, L. Roy, H. Gurler, J. Xie, D.D. Lantvit, H. Cardenas, F. Fang, Y. Liu, E. Loughran, J. Yang, M. Sharon Stack, R.E. Emerson, K.D. Cowden, V.B. Dahl, K.P. M, D. Nephew, Matei, J.E. Burdette, In vivo tumor growth of high-grade serous ovarian cancer cell lines. Gynecol. Oncol. 138, 372–377 (2015)CrossRef A.K. Mitra, D.A. Davis, S. Tomar, L. Roy, H. Gurler, J. Xie, D.D. Lantvit, H. Cardenas, F. Fang, Y. Liu, E. Loughran, J. Yang, M. Sharon Stack, R.E. Emerson, K.D. Cowden, V.B. Dahl, K.P. M, D. Nephew, Matei, J.E. Burdette, In vivo tumor growth of high-grade serous ovarian cancer cell lines. Gynecol. Oncol. 138, 372–377 (2015)CrossRef
30.
Zurück zum Zitat C.R. Cochrane, A. Szczepny, D.N. Watkins, J.E. Cain, Hedgehog signaling in the maintenance of cancer stem cells. Cancers (Basel) 7, 1554–1585 (2015)CrossRef C.R. Cochrane, A. Szczepny, D.N. Watkins, J.E. Cain, Hedgehog signaling in the maintenance of cancer stem cells. Cancers (Basel) 7, 1554–1585 (2015)CrossRef
31.
Zurück zum Zitat V.J. Guen, T.E. Chavarria, C. Kroger, X. Ye, R.A. Weinberg, J.A. Lees, EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. Proc. Natl. Acad. Sci. U. S. A. 114, E10532-E10539 (2017) V.J. Guen, T.E. Chavarria, C. Kroger, X. Ye, R.A. Weinberg, J.A. Lees, EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. Proc. Natl. Acad. Sci. U. S. A. 114, E10532-E10539 (2017)
32.
Zurück zum Zitat A. Ray, E. Meng, E. Reed, L.A. Shevde, R.P. Rocconi, Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int. J. Oncol. 39, 797–804 (2011)PubMed A. Ray, E. Meng, E. Reed, L.A. Shevde, R.P. Rocconi, Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int. J. Oncol. 39, 797–804 (2011)PubMed
33.
Zurück zum Zitat P. Ozretic, D. Trnski, V. Musani, I. Maurac, D. Kalafatic, S. Oreskovic, S. Levanat, M. Sabol, Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas. Int. J. Oncol. 51, 1869–1877 (2017)CrossRef P. Ozretic, D. Trnski, V. Musani, I. Maurac, D. Kalafatic, S. Oreskovic, S. Levanat, M. Sabol, Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas. Int. J. Oncol. 51, 1869–1877 (2017)CrossRef
34.
Zurück zum Zitat A. Ciucci, I. De Stefano, V.G. Vellone, L. Lisi, C. Bottoni, G. Scambia, G.F. Zannoni, D. Gallo, Expression of the glioma-associated oncogene homolog 1 (gli1) in advanced serous ovarian cancer is associated with unfavorable overall survival. PLoS One 8, e60145 (2013) A. Ciucci, I. De Stefano, V.G. Vellone, L. Lisi, C. Bottoni, G. Scambia, G.F. Zannoni, D. Gallo, Expression of the glioma-associated oncogene homolog 1 (gli1) in advanced serous ovarian cancer is associated with unfavorable overall survival. PLoS One 8, e60145 (2013)
35.
Zurück zum Zitat X. Li, W. Deng, S.M. Lobo-Ruppert, J.M. Ruppert, Gli1 acts through Snail and E-cadherin to promote nuclear signaling by beta-catenin. Oncogene 26, 4489–4498 (2007)CrossRef X. Li, W. Deng, S.M. Lobo-Ruppert, J.M. Ruppert, Gli1 acts through Snail and E-cadherin to promote nuclear signaling by beta-catenin. Oncogene 26, 4489–4498 (2007)CrossRef
36.
Zurück zum Zitat J. Li, J. Cai, S. Zhao, K. Yao, Y. Sun, Y. Li, L. Chen, R. Li, X. Zhai, J. Zhang, C. Jiang, GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment. J. Exp. Clin. Cancer Res. 35, 184 (2016)CrossRef J. Li, J. Cai, S. Zhao, K. Yao, Y. Sun, Y. Li, L. Chen, R. Li, X. Zhai, J. Zhang, C. Jiang, GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment. J. Exp. Clin. Cancer Res. 35, 184 (2016)CrossRef
37.
Zurück zum Zitat The Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011) The Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011)
38.
Zurück zum Zitat J. Zhang, Z.Y. Li, X.J. Duan, X.M. Fan, W.N. Liu, Y.H. Li, [Clinical significance of FOXM1 and Gli-1 protein expression in high-grade ovarian serous carcinoma]. Zhonghua Zhong Liu Za Zhi 38, 904–908 (2016)PubMed J. Zhang, Z.Y. Li, X.J. Duan, X.M. Fan, W.N. Liu, Y.H. Li, [Clinical significance of FOXM1 and Gli-1 protein expression in high-grade ovarian serous carcinoma]. Zhonghua Zhong Liu Za Zhi 38, 904–908 (2016)PubMed
39.
Zurück zum Zitat Q. Li, R.K. Lex, H. Chung, S.M. Giovanetti, Z. Ji, H. Ji, M.D. Person, J. Kim, S.A. Vokes, The pluripotency factor NANOG binds to GLI proteins and represses hedgehog-mediated transcription. J. Biol. Chem. 291, 7171–7182 (2016)CrossRef Q. Li, R.K. Lex, H. Chung, S.M. Giovanetti, Z. Ji, H. Ji, M.D. Person, J. Kim, S.A. Vokes, The pluripotency factor NANOG binds to GLI proteins and represses hedgehog-mediated transcription. J. Biol. Chem. 291, 7171–7182 (2016)CrossRef
40.
Zurück zum Zitat M. Ding, X. Wang, Antagonism between Hedgehog and Wnt signaling pathways regulates tumorigenicity. Oncol. Lett. 14, 6327–6333 (2017)PubMedPubMedCentral M. Ding, X. Wang, Antagonism between Hedgehog and Wnt signaling pathways regulates tumorigenicity. Oncol. Lett. 14, 6327–6333 (2017)PubMedPubMedCentral
41.
Zurück zum Zitat J. Reda, J. Vachtenheim, K. Vlckova, P. Horak, J. Vachtenheim Jr., L. Ondrusova, Widespread expression of hedgehog pathway components in a large panel of human tumor cells and inhibition of tumor growth by GANT61: implications for cancer therapy. Int. J. Mol. Sci. 19, (2018) J. Reda, J. Vachtenheim, K. Vlckova, P. Horak, J. Vachtenheim Jr., L. Ondrusova, Widespread expression of hedgehog pathway components in a large panel of human tumor cells and inhibition of tumor growth by GANT61: implications for cancer therapy. Int. J. Mol. Sci. 19, (2018)
42.
Zurück zum Zitat A. Po, M. Silvano, E. Miele, C. Capalbo, A. Eramo, V. Salvati, M. Todaro, Z.M. Besharat, G. Catanzaro, D. Cucchi, S. Coni, L. Di Marcotullio, G. Canettieri, A. Vacca, G. Stassi, E. De Smaele, M. Tartaglia, I. Screpanti, R. De Maria, E. Ferretti, Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma. Oncogene 36, 4641–4652 (2017)CrossRef A. Po, M. Silvano, E. Miele, C. Capalbo, A. Eramo, V. Salvati, M. Todaro, Z.M. Besharat, G. Catanzaro, D. Cucchi, S. Coni, L. Di Marcotullio, G. Canettieri, A. Vacca, G. Stassi, E. De Smaele, M. Tartaglia, I. Screpanti, R. De Maria, E. Ferretti, Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma. Oncogene 36, 4641–4652 (2017)CrossRef
43.
Zurück zum Zitat N. Li, S. Truong, M. Nouri, J. Moore, N. Al Nakouzi, A.A. Lubik, R. Buttyan, Non-canonical activation of hedgehog in prostate cancer cells mediated by the interaction of transcriptionally active androgen receptor proteins with Gli3. Oncogene 37, 2313–2325 (2018)CrossRef N. Li, S. Truong, M. Nouri, J. Moore, N. Al Nakouzi, A.A. Lubik, R. Buttyan, Non-canonical activation of hedgehog in prostate cancer cells mediated by the interaction of transcriptionally active androgen receptor proteins with Gli3. Oncogene 37, 2313–2325 (2018)CrossRef
44.
Zurück zum Zitat A. Sanchez-Danes, J.C. Larsimont, M. Liagre, E. Munoz-Couselo, G. Lapouge, A. Brisebarre, C. Dubois, M. Suppa, V. Sukumaran, V. Del Marmol, J. Tabernero, C. Blanpain, A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy. Nature 562, 434–438 (2018)CrossRef A. Sanchez-Danes, J.C. Larsimont, M. Liagre, E. Munoz-Couselo, G. Lapouge, A. Brisebarre, C. Dubois, M. Suppa, V. Sukumaran, V. Del Marmol, J. Tabernero, C. Blanpain, A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy. Nature 562, 434–438 (2018)CrossRef
45.
Zurück zum Zitat J. Rodriguez-Blanco, L. Pednekar, C. Penas, B. Li, V. Martin, J. Long, E. Lee, W.A. Weiss, C. Rodriguez, N. Mehrdad, D.M. Nguyen, N.G. Ayad, P. Rai, A.J. Capobianco, D.J. Robbins, Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma. Oncogene 36, 6306–6314 (2017)CrossRef J. Rodriguez-Blanco, L. Pednekar, C. Penas, B. Li, V. Martin, J. Long, E. Lee, W.A. Weiss, C. Rodriguez, N. Mehrdad, D.M. Nguyen, N.G. Ayad, P. Rai, A.J. Capobianco, D.J. Robbins, Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma. Oncogene 36, 6306–6314 (2017)CrossRef
46.
Zurück zum Zitat J. Gao, S. Graves, U. Koch, S. Liu, V. Jankovic, S. Buonamici, A. El Andaloussi, S.D. Nimer, B.L. Kee, R. Taichman, F. Radtke, I. Aifantis, Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 4, 548–558 (2009)CrossRef J. Gao, S. Graves, U. Koch, S. Liu, V. Jankovic, S. Buonamici, A. El Andaloussi, S.D. Nimer, B.L. Kee, R. Taichman, F. Radtke, I. Aifantis, Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 4, 548–558 (2009)CrossRef
Metadaten
Titel
The hedgehog pathway regulates cancer stem cells in serous adenocarcinoma of the ovary
verfasst von
Smarakan Sneha
Rohit P. Nagare
Chirukandath Sidhanth
Syama Krishnapriya
Manoj Garg
Balaji Ramachandran
Kanchan Murhekar
Shirley Sundersingh
Trivadi S. Ganesan
Publikationsdatum
08.05.2020
Verlag
Springer Netherlands
Erschienen in
Cellular Oncology / Ausgabe 4/2020
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-020-00504-w

Neu im Fachgebiet Pathologie

Pathologie der Milz

Nach einer Beschreibung der Milzanatomie und Darstellung der diagnostisch wichtigsten immunhistochemischen Färbungen zur Identifizierung der normalen Milzkompartimente werden am Beispiel eines nordafrikanischen Patienten mit rezentem …

Molekular definierte Nierenzellkarzinome 2025

Im Zuge der Überarbeitung der WHO-Klassifikation im Jahr 2022 konnten für mehrere Nierenzellkarzinome (NZK), die sich zuvor nicht eindeutig den bis dahin definierten Tumortypen zuordnen ließen, jedoch gemeinsame morphologische und molekulare …

Wichtige Änderungen in der WHO-Klassifikation der Hodentumoren 2022

In der 5. Auflage der „WHO-Klassifikation der Tumoren der ableitenden Harnwege und des männlichen Genitaltrakts“ sind bedeutende Anpassungen an den bisherigen Klassifikationen vorgenommen worden. Diese betreffen bei den Keimzelltumoren des Hodens …

DNA mixture deconvolution using fully continuous models EuroForMix and EFMrep

  • Open Access
  • Originalien

Mixture deconvolution is a powerful tool for inferring individual DNA profiles from DNA mixtures for subsequent transmission to a database or database queries. To carry out deconvolution, a mixed trace can be interpreted either manually by an …