Skip to main content
Top
Published in: Medical Oncology 1/2015

01-01-2015 | Original Paper

Sonic hedgehog–Gli1 signals promote epithelial–mesenchymal transition in ovarian cancer by mediating PI3K/AKT pathway

Authors: Zhang Ke, Sun Caiping, Zhang Qing, Wang Xiaojing

Published in: Medical Oncology | Issue 1/2015

Login to get access

Abstract

Epithelial–mesenchymal transition (EMT) has been reported to play an important role in distant metastasis in cancer-related disease. A large number of studies have shown that sonic hedgehog–glioma-associated oncogene 1 (Shh–Gli1) signals participate in the process of EMT; however, the role and mechanism of Shh–Gli1 signals in the progression of EMT in ovarian cancer remain largely unknown. First, we investigated the occurrence of EMT and invasion and migration ability in ovarian cancer cells stimulated by different concentration of Shh–Gli1 signals agonist purmorphamine in vitro. Then, Akt siRNA was transfected into ovarian cancer cells which already stimulated by purmorphamine to elucidate the molecular mechanism underlying the pathogenesis of EMT in ovarian cancer. Gli1 expression was significantly enhanced in ovarian cancer cells after stimulated by purmorphamine. In addition, Gli1 up-regulation promoted EMT, invasion and migration ability of ovarian cancer cells. Furthermore, we validated a cross talk between Shh–Gli1 signals and PI3K–Akt pathway in the occurrence of EMT in ovarian cancer cells. These findings revealed a novel role for Shh–Gli1 signals in EMT in ovarian cancer and provided for us a potential therapeutic target for the suppression of EMT, invasion and metastasis in ovarian cancer.
Literature
1.
go back to reference Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, Thiery JP. Epithelial–mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 2014;6(10):1279–93.PubMedCentralPubMedCrossRef Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, Thiery JP. Epithelial–mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 2014;6(10):1279–93.PubMedCentralPubMedCrossRef
2.
go back to reference Wang Y, Hu C, Dong R, Huang X, Qiu H. Platelet-derived growth factor-D promotes ovarian cancer invasion by regulating matrix metalloproteinases 2 and 9. Asian Pac J Cancer Prev. 2011;12(12):3367–70.PubMed Wang Y, Hu C, Dong R, Huang X, Qiu H. Platelet-derived growth factor-D promotes ovarian cancer invasion by regulating matrix metalloproteinases 2 and 9. Asian Pac J Cancer Prev. 2011;12(12):3367–70.PubMed
3.
go back to reference Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB, Lin X. Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep. 2014;32(5):2150–8.PubMed Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB, Lin X. Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep. 2014;32(5):2150–8.PubMed
4.
go back to reference Wang WS, Yang XS, Xia M, Jiang HY, Hou JQ. Silencing of twist expression by RNA interference suppresses epithelial–mesenchymal transition, invasion, and metastasis of ovarian cancer. Asian Pac J Cancer Prev. 2012;13(9):4435–9.PubMedCrossRef Wang WS, Yang XS, Xia M, Jiang HY, Hou JQ. Silencing of twist expression by RNA interference suppresses epithelial–mesenchymal transition, invasion, and metastasis of ovarian cancer. Asian Pac J Cancer Prev. 2012;13(9):4435–9.PubMedCrossRef
5.
go back to reference Law AY, Wong CK. Stanniocalcin-2 promotes epithelial–mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp Cell Res. 2010;316(20):3425–34.PubMedCrossRef Law AY, Wong CK. Stanniocalcin-2 promotes epithelial–mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp Cell Res. 2010;316(20):3425–34.PubMedCrossRef
6.
go back to reference Yun SJ, Kim WJ. Role of the epithelial–mesenchymal transition in bladder cancer: from prognosis to therapeutic target. Korean J Urol. 2013;54(10):645–50.PubMedCentralPubMedCrossRef Yun SJ, Kim WJ. Role of the epithelial–mesenchymal transition in bladder cancer: from prognosis to therapeutic target. Korean J Urol. 2013;54(10):645–50.PubMedCentralPubMedCrossRef
7.
go back to reference Xu X, Su B, Xie C, Wei S, Zhou Y, Liu H, Dai W, Cheng P, Wang F, Xu X, Guo C. Sonic hedgehog–Gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells. PLoS One. 2014;9(7):e96441.PubMedCentralPubMedCrossRef Xu X, Su B, Xie C, Wei S, Zhou Y, Liu H, Dai W, Cheng P, Wang F, Xu X, Guo C. Sonic hedgehog–Gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells. PLoS One. 2014;9(7):e96441.PubMedCentralPubMedCrossRef
8.
go back to reference Sun XD, Liu XE, Huang DS. Curcumin reverses the epithelial–mesenchymal transition of pancreatic cancer cells by inhibiting the Hedgehog signaling pathway. Oncol Rep. 2013;29(6):2401–7.PubMed Sun XD, Liu XE, Huang DS. Curcumin reverses the epithelial–mesenchymal transition of pancreatic cancer cells by inhibiting the Hedgehog signaling pathway. Oncol Rep. 2013;29(6):2401–7.PubMed
9.
go back to reference Clark AR, Toker A. Signalling specificity in the Akt pathway in breast cancer. Biochem Soc Trans. 2014;42(5):1349–55.PubMedCrossRef Clark AR, Toker A. Signalling specificity in the Akt pathway in breast cancer. Biochem Soc Trans. 2014;42(5):1349–55.PubMedCrossRef
10.
go back to reference Xu X, Zhou Y, Xie C, Wei SM, Gan H, He S, Wang F, Xu L, Lu J, Dai W, He L, Chen P, Wang X, Guo C. Genome-wide screening reveals an EMT molecular network mediated by sonic hedgehog–Gli1 signaling in pancreatic cancer cells. PLoS One. 2012;7(8):e43119.PubMedCentralPubMedCrossRef Xu X, Zhou Y, Xie C, Wei SM, Gan H, He S, Wang F, Xu L, Lu J, Dai W, He L, Chen P, Wang X, Guo C. Genome-wide screening reveals an EMT molecular network mediated by sonic hedgehog–Gli1 signaling in pancreatic cancer cells. PLoS One. 2012;7(8):e43119.PubMedCentralPubMedCrossRef
11.
go back to reference Wang ZM, Lu YK, Han Y, Jiang JY, Yuan XD. Dipeptidyl peptidase IV gene expression in ovarian carcinoma cell lines with various malignant behaviour. Acta Academiae Medicinae Sinicae. 2005;27(2):205–10.PubMed Wang ZM, Lu YK, Han Y, Jiang JY, Yuan XD. Dipeptidyl peptidase IV gene expression in ovarian carcinoma cell lines with various malignant behaviour. Acta Academiae Medicinae Sinicae. 2005;27(2):205–10.PubMed
12.
go back to reference Hua F, Xia Y, Wang H, Chen R, Ren Y, Yang J, Liang W. Effects of small interfering RNA silencing MACC-1 expression on cell proliferation, cell cycle and invasion ability of cervical cancer SiHa cells. Zhonghua Zhong Liu Za Zhi. 2014;36(7):496–500.PubMed Hua F, Xia Y, Wang H, Chen R, Ren Y, Yang J, Liang W. Effects of small interfering RNA silencing MACC-1 expression on cell proliferation, cell cycle and invasion ability of cervical cancer SiHa cells. Zhonghua Zhong Liu Za Zhi. 2014;36(7):496–500.PubMed
13.
go back to reference Wolff F, Loipetzberger A, Gruber W, Esterbauer H, Aberger F, Frischauf AM. Imiquimod directly inhibits Hedgehog signalling by stimulating adenosine receptor/protein kinase A-mediated GLI phosphorylation. Oncogene. 2013;32(50):5574–81.PubMedCentralPubMedCrossRef Wolff F, Loipetzberger A, Gruber W, Esterbauer H, Aberger F, Frischauf AM. Imiquimod directly inhibits Hedgehog signalling by stimulating adenosine receptor/protein kinase A-mediated GLI phosphorylation. Oncogene. 2013;32(50):5574–81.PubMedCentralPubMedCrossRef
14.
go back to reference Davidson B, Rosenfeld YB, Holth A, Hellesylt E, Tropé CG, Reich R, Yisraeli JK. VICKZ2 protein expression in ovarian serous carcinoma effusions is associated with poor survival. Hum Pathol. 2014;45(7):1520–8.PubMedCrossRef Davidson B, Rosenfeld YB, Holth A, Hellesylt E, Tropé CG, Reich R, Yisraeli JK. VICKZ2 protein expression in ovarian serous carcinoma effusions is associated with poor survival. Hum Pathol. 2014;45(7):1520–8.PubMedCrossRef
15.
go back to reference Oue T, Uehara S, Yamanaka H, Nomura M, Usui N. Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells. Pediatr Surg Int. 2013;29(11):1153–8.PubMedCentralPubMedCrossRef Oue T, Uehara S, Yamanaka H, Nomura M, Usui N. Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells. Pediatr Surg Int. 2013;29(11):1153–8.PubMedCentralPubMedCrossRef
16.
go back to reference Javelaud D, Pierrat MJ, Mauviel A. Crosstalk between TGF-β and hedgehog signaling in cancer. FEBS Lett. 2012;586(14):2016–25.PubMedCrossRef Javelaud D, Pierrat MJ, Mauviel A. Crosstalk between TGF-β and hedgehog signaling in cancer. FEBS Lett. 2012;586(14):2016–25.PubMedCrossRef
17.
go back to reference Yanai K, Nakamura M, Akiyoshi T, Nagai S, Wada J, Koga K, Noshiro H, Nagai E, Tsuneyoshi M, Tanaka M, Katano M. Crosstalk of hedgehog and Wnt pathways in gastric cancer. Cancer Lett. 2008;263(1):145–56.PubMedCrossRef Yanai K, Nakamura M, Akiyoshi T, Nagai S, Wada J, Koga K, Noshiro H, Nagai E, Tsuneyoshi M, Tanaka M, Katano M. Crosstalk of hedgehog and Wnt pathways in gastric cancer. Cancer Lett. 2008;263(1):145–56.PubMedCrossRef
18.
go back to reference Min S, Xiaoyan X, Fanghui P, Yamei W, Xiaoli Y, Feng W. The glioma-associated oncogene homolog 1 promotes epithelial–mesenchymal transition in human esophageal squamous cell cancer by inhibiting E-cadherin via snail. Cancer Gene Ther. 2013;20(7):379–85.PubMedCrossRef Min S, Xiaoyan X, Fanghui P, Yamei W, Xiaoli Y, Feng W. The glioma-associated oncogene homolog 1 promotes epithelial–mesenchymal transition in human esophageal squamous cell cancer by inhibiting E-cadherin via snail. Cancer Gene Ther. 2013;20(7):379–85.PubMedCrossRef
19.
go back to reference Busch EL, McGraw KA, Sandler RS. The potential for markers of epithelial–mesenchymal transition to improve colorectal cancer outcomes: a systematic review. Cancer Epidemiol Biomark Prev. 2014;23(7):1164–75.CrossRef Busch EL, McGraw KA, Sandler RS. The potential for markers of epithelial–mesenchymal transition to improve colorectal cancer outcomes: a systematic review. Cancer Epidemiol Biomark Prev. 2014;23(7):1164–75.CrossRef
20.
go back to reference Xuan X, Zeng Q, Li Y, Gao Y, Wang F, Zhang H, Wang Z, He H, Li S. Akt-mediated transforming growth factor-β1-induced epithelial–mesenchymal transition in cultured human esophageal squamous cancer cells. Cancer Gene Ther. 2014;21(6):238–45.PubMedCrossRef Xuan X, Zeng Q, Li Y, Gao Y, Wang F, Zhang H, Wang Z, He H, Li S. Akt-mediated transforming growth factor-β1-induced epithelial–mesenchymal transition in cultured human esophageal squamous cancer cells. Cancer Gene Ther. 2014;21(6):238–45.PubMedCrossRef
21.
go back to reference Kuo SZ, Blair KJ, Rahimy E, Kiang A, Abhold E, Fan JB, Wang-Rodriguez J, Altuna X, Ongkeko WM. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt. BMC Cancer. 2012;12:556–63.PubMedCentralPubMedCrossRef Kuo SZ, Blair KJ, Rahimy E, Kiang A, Abhold E, Fan JB, Wang-Rodriguez J, Altuna X, Ongkeko WM. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt. BMC Cancer. 2012;12:556–63.PubMedCentralPubMedCrossRef
Metadata
Title
Sonic hedgehog–Gli1 signals promote epithelial–mesenchymal transition in ovarian cancer by mediating PI3K/AKT pathway
Authors
Zhang Ke
Sun Caiping
Zhang Qing
Wang Xiaojing
Publication date
01-01-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0368-y

Other articles of this Issue 1/2015

Medical Oncology 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine