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Article

Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4

  • Authors:
    • Teng Hua
    • Xiaoxiao Wang
    • Shuqi Chi
    • Yan Liu
    • Dilu Feng
    • Yingchao Zhao
    • Hongbo Wang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China
  • Pages: 823-832
    |
    Published online on: June 4, 2018
       https://doi.org/10.3892/or.2018.6471
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Abstract

S100 calcium binding protein A4 (S100A4) is a well‑established tumor metastasis mediator in various malignancies, including endometrial cancer (EC). However, the regulatory mechanism underlying S100A4 expression remains elusive. In the present study, by analyzing public datasets and clinical samples, we found that estrogen‑related receptor γ (ERRγ) was upregulated and positively correlated with S100A4 transcription in EC. ERRγ knockdown inhibited S100A4 expression and promoted the expression of its downstream target E‑cadherin, and vice versa. Mechanistic studies indicated that ERRγ enhanced the promoter activity of S100A4 to facilitate its transcription. In addition, knockdown of ERRγ suppressed migration and invasion of EC cells in vitro, while ectopic ERRγ expression promoted migration and invasion of EC cells in vitro and tumor growth in vivo. Importantly, restoration of S100A4 expression prevented EC cells from undergoing ERRγ‑mediated changes in these biological features. In addition, synchronous changes in S100A4 and ERRγ expression were observed after incubation with estrogen. Overall, ERRγ may exert oncogenic activity mainly associated with aggressiveness of EC by activating S100A4 transcription and thus may be a novel therapeutic target in EC.
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1 

Morice P, Leary A, Creutzberg C, Abu-Rustum N and Darai E: Endometrial cancer. Lancet. 387:1094–1108. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Makker A and Goel MM: Tumor progression, metastasis, and modulators of epithelial-mesenchymal transition in endometrioid endometrial carcinoma: An update. Endocr Relat Cancer. 23:R85–R111. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ and Geczy CL: Functions of S100 proteins. Curr Mol Med. 13:24–57. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Stewart RL and O'Connor KL: Clinical significance of the integrin α6β4 in human malignancies. Lab Invest. 95:976–986. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Kiss B, Kalmar L, Nyitray L and Pal G: Structural determinants governing S100A4-induced isoform-selective disassembly of nonmuscle myosin II filaments. FEBS J. 283:2164–2180. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Dahlmann M, Kobelt D, Walther W, Mudduluru G and Stein U: S100A4 in cancer metastasis: Wnt signaling-driven interventions for metastasis restriction. Cancers. 8:pii: E59. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Bresnick AR, Weber DJ and Zimmer DB: S100 proteins in cancer. Nat Rev Cancer. 15:96–109. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Hua T, Liu S, Xin X, Cai L, Shi R, Chi S, Feng D and Wang H: S100A4 promotes endometrial cancer progress through epithelial-mesenchymal transition regulation. Oncol Rep. 35:3419–3426. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Deblois G and Giguere V: Functional and physiological genomics of estrogen-related receptors (ERRs) in health and disease. Biochim Biophys Acta. 1812:1032–1040. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Ranhotra HS: The orphan estrogen-related receptor alpha and metabolic regulation: New frontiers. J Recept Signal Transduct Res. 35:565–568. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Madhavan S, Gusev Y, Singh S and Riggins RB: ERRgamma target genes are poor prognostic factors in Tamoxifen-treated breast cancer. J Exp Clin Cancer Res. 34:452015. View Article : Google Scholar : PubMed/NCBI

13 

Misawa A and Inoue S: Estrogen-Related Receptors in Breast Cancer and Prostate Cancer. Front Endocrinol. 6:832015. View Article : Google Scholar

14 

Gao M, Sun P, Wang J, Zhao D and Wei L: Expression of estrogen receptor-related receptor isoforms and clinical significance in endometrial adenocarcinoma. Int J Gynecol Cancer. 16:827–833. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Yamamoto T, Mori T, Sawada M, Kuroboshi H, Tatsumi H, Yoshioka T, Matsushima H, Iwasaku K and Kitawaki J: Estrogen-related receptor-gamma regulates estrogen receptor-alpha responsiveness in uterine endometrial cancer. Int J Gynecol Cancer. 22:1509–1516. 2012.PubMed/NCBI

16 

Sun Y, Wang C, Yang H and Ma X: The effect of estrogen on the proliferation of endometrial cancer cells is mediated by ERRgamma through AKT and ERK1/2. Eur J Cancer Prev. 23:418–424. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Huang S, Zheng J, Huang Y, Song L, Yin Y, Ou D, He S, Chen X and Ouyang X: Impact of S100A4 expression on clinicopathological characteristics and prognosis in pancreatic cancer: A meta-analysis. Dis Markers. 2016:81373782016. View Article : Google Scholar : PubMed/NCBI

18 

Ling Z and Li R: Clinicopathological and prognostic value of S100A4 expression in gastric cancer: A meta-analysis. Int J Biol Markers. 29:e99–e111. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Stewart RL, Carpenter BL, West DS, Knifley T, Liu L, Wang C, Weiss HL, Gal TS, Durbin EB, Arnold SM, et al: S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide. Oncotarget. 7:34630–34642. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Dou C, Liu Z, Xu M, Jia Y, Wang Y, Li Q, Yang W, Zheng X, Tu K and Liu Q: miR-187-3p inhibits the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting S100A4. Cancer Lett. 381:380–390. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Hernan R, Fasheh R, Calabrese C, Frank AJ, Maclean KH, Allard D, Barraclough R and Gilbertson RJ: ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res. 63:140–148. 2003.PubMed/NCBI

22 

Kim TH, Kim HI, Soung YH, Shaw LA and Chung J: Integrin (alpha6beta4) signals through Src to increase expression of S100A4, a metastasis-promoting factor: Implications for cancer cell invasion. Mol Cancer Res. 7:1605–1612. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Wang H, Shi J, Luo Y, Liao Q, Niu Y, Zhang F, Shao Z, Ding Y and Zhao L: LIM and SH3 protein 1 induces TGFbeta-mediated epithelial-mesenchymal transition in human colorectal cancer by regulating S100A4 expression. Clin Cancer Res. 20:5835–5847. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Huss JM, Garbacz WG and Xie W: Constitutive activities of estrogen-related receptors: Transcriptional regulation of metabolism by the ERR pathways in health and disease. Biochim Biophys Acta. 1852:1912–1927. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Deblois G, St-Pierre J and Giguere V: The PGC-1/ERR signaling axis in cancer. Oncogene. 32:3483–3490. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Giguere V: To ERR in the estrogen pathway. Trends Endocrinol Metab. 13:220–225. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Sun P, Sehouli J, Denkert C, Mustea A, Könsgen D, Koch I, Wei L and Lichtenegger W: Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells. J Mol Med. 83:457–467. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Audet-Walsh E, Yee T, McGuirk S, Vernier M, Ouellet C, St-Pierre J and Giguère V: Androgen-dependent repression of errgamma reprograms metabolism in prostate cancer. Cancer Res. 77:378–389. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Kim JH, Choi YK, Byun JK, Kim MK, Kang YN, Kim SH, Lee S, Jang BK and Park KG: Estrogen-related receptor gamma is upregulated in liver cancer and its inhibition suppresses liver cancer cell proliferation via induction of p21 and p27. Exp Mol Med. 48:e2132016. View Article : Google Scholar : PubMed/NCBI

30 

Huppunen J and Aarnisalo P: Dimerization modulates the activity of the orphan nuclear receptor ERRgamma. Biochem Biophys Res Commun. 314:964–970. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D and Renaud JP: Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell. 9:303–313. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Audet-Walsh E and Giguere V: The multiple universes of estrogen-related receptor α and γ in metabolic control and related diseases. Acta Pharmacol Sin. 36:51–61. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Eichner LJ, Perry MC, Dufour CR, Bertos N, Park M, St-Pierre J and Giguère V: miR-378* mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway. Cell Metab. 12:352–361. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Tiraby C, Hazen BC, Gantner ML and Kralli A: Estrogen-related receptor gamma promotes mesenchymal-to-epithelial transition and suppresses breast tumor growth. Cancer Res. 71:2518–2528. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Ijichi N, Shigekawa T, Ikeda K, Horie-Inoue K, Fujimura T, Tsuda H, Osaki A, Saeki T and Inoue S: Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer. J Steroid Biochem Mol Biol. 123:1–7. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Jeon SY, Hwang KA and Choi KC: Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development. J Steroid Biochem Mol Biol. 158:1–8. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Sun Y, Wang Y, Fan C, Gao P, Wang X, Wei G and Wei J: Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells through Gli1 activation. Mol Cancer. 13:1372014. View Article : Google Scholar : PubMed/NCBI

38 

Day RS, McDade KK, Chandran UR, Lisovich A, Conrads TP, Hood BL, Kolli VS, Kirchner D, Litzi T and Maxwell GL: Identifier mapping performance for integrating transcriptomics and proteomics experimental results. BMC Bioinformatics. 12:2132011. View Article : Google Scholar : PubMed/NCBI

39 

Pappa KI, Polyzos A, Jacob-Hirsch J, Amariglio N, Vlachos GD, Loutradis D and Anagnou NP: Profiling of discrete gynecological cancers reveals novel transcriptional modules and common features shared by other cancer types and embryonic stem cells. PLoS One. 10:e01422292015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hua T, Wang X, Chi S, Liu Y, Feng D, Zhao Y and Wang H: Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4. Oncol Rep 40: 823-832, 2018.
APA
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., & Wang, H. (2018). Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4. Oncology Reports, 40, 823-832. https://doi.org/10.3892/or.2018.6471
MLA
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., Wang, H."Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4". Oncology Reports 40.2 (2018): 823-832.
Chicago
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., Wang, H."Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4". Oncology Reports 40, no. 2 (2018): 823-832. https://doi.org/10.3892/or.2018.6471
Copy and paste a formatted citation
x
Spandidos Publications style
Hua T, Wang X, Chi S, Liu Y, Feng D, Zhao Y and Wang H: Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4. Oncol Rep 40: 823-832, 2018.
APA
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., & Wang, H. (2018). Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4. Oncology Reports, 40, 823-832. https://doi.org/10.3892/or.2018.6471
MLA
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., Wang, H."Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4". Oncology Reports 40.2 (2018): 823-832.
Chicago
Hua, T., Wang, X., Chi, S., Liu, Y., Feng, D., Zhao, Y., Wang, H."Estrogen‑related receptor γ promotes the migration and metastasis of endometrial cancer cells by targeting S100A4". Oncology Reports 40, no. 2 (2018): 823-832. https://doi.org/10.3892/or.2018.6471
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