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Article Open Access

STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer

  • Authors:
    • Yao Cui
    • Yun-Yun Li
    • Jian Li
    • Hong-Yan Zhang
    • Feng Wang
    • Xue Bai
    • Shan-Shan Li
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of General Surgery, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China
    Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 108-116
    |
    Published online on: May 19, 2016
       https://doi.org/10.3892/or.2016.4822
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Abstract

Hypoxia plays a key role in tumour initiation and metastasis; one of the mechanisms is to induce epithelial-mesenchymal transition (EMT). Signal transducer and activator of transcription 3 (STAT3) is involved in EMT by regulating the transcriptional regulators of E-cadherin, the biomarker of EMT. Until now, however, few studies have focused on the effects of STAT3 in hypoxia-induced EMT in tumour cells. The goal of this study was to investigate the roles of STAT3 in hypoxia-induced EMT in oesophageal squamous cell carcinoma (ESCC). The ESCC cells, TE-1 and EC-1, were incubated in normoxia, or in CoCl2, which was used to mimic hypoxia. With CoCl2, the ESCC cells showed increased migration and invasion abilities, accompanied with upregulation of HIF-1α, STAT3, and vimentin, and downregulation of E-cadherin. Knockdown of STAT3 inhibited EMT of ESCC cells and downregulated HIF-1α in vitro and in vivo. In ChIP assays, STAT3 bound to the promoter of HIF-1α, suggesting that STAT3 regulates transcription of HIF-1α. In conclusion, hypoxia induces EMT of ESCC, and STAT3 regulates this process by promoting HIF-1α expression.
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1 

Książkiewicz M, Markiewicz A and Zaczek AJ: Epithelial-mesenchymal transition: A hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology. 79:195–208. 2012. View Article : Google Scholar

2 

Tania M, Khan MA and Fu J: Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer. Tumour Biol. 35:7335–7342. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Imai T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T and Konishi I: Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol. 163:1437–1447. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Philip B, Ito K, Moreno-Sánchez R and Ralph SJ: HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression. Carcinogenesis. 34:1699–1707. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Yoo YG, Christensen J, Gu J and Huang LE: HIF-1α mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progression. Sci Signal. 4:pt42011. View Article : Google Scholar

6 

Sahlgren C, Gustafsson MV, Jin S, Poellinger L and Lendahl U: Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA. 105:6392–6397. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Copple BL: Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms. Liver Int. 30:669–682. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Li GQ, Zhang Y, Liu D, Qian YY, Zhang H, Guo SY, Sunagawa M, Hisamitsu T and Liu YQ: PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol Cell Biochem. 372:221–231. 2013. View Article : Google Scholar

9 

Zhang Q, Bai X, Chen W, Ma T, Hu Q, Liang C, Xie S, Chen C, Hu L, Xu S, et al: Wnt/β-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling. Carcinogenesis. 34:962–973. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Percio S, Coltella N, Grisanti S, Bernardi R and Pattini L: A HIF-1 network reveals characteristics of epithelial-mesenchymal transition in acute promyelocytic leukemia. Genome Med. 6(84)2014. View Article : Google Scholar : PubMed/NCBI

11 

Brierley MM and Fish EN: STATs: Multifaceted regulators of transcription. J Interferon Cytokine Res. 25:733–744. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Zhao S, Venkatasubbarao K, Lazor JW, Sperry J, Jin C, Cao L and Freeman JW: Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res. 68:4221–4228. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Colomiere M, Ward AC, Riley C, Trenerry MK, Cameron-Smith D, Findlay J, Ackland L and Ahmed N: Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer. 100:134–144. 2009. View Article : Google Scholar

14 

Cho KH, Choi MJ, Jeong KJ, Kim JJ, Hwang MH, Shin SC, Park CG and Lee HY: A ROS/STAT3/HIF-1α signaling cascade mediates EGF-induced TWIST1 expression and prostate cancer cell invasion. Prostate. 74:528–536. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lo HW, Hsu SC, Xia W, Cao X, Shih JY, Wei Y, Abbruzzese JL, Hortobagyi GN and Hung MC: Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res. 67:9066–9076. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Huang C, Yang G, Jiang T, Zhu G, Li H and Qiu Z: The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro. Neoplasma. 58:396–405. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Xiong H, Hong J, Du W, Lin YW, Ren LL, Wang YC, Su WY, Wang JL, Cui Y, Wang ZH, et al: Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem. 287:5819–5832. 2012. View Article : Google Scholar :

18 

Hu QD, Chen W, Yan TL, Ma T, Chen CL, Liang C, Zhang Q, Xia XF, Liu H, Zhi X, et al: NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial-mesenchymal transition in hepatocellular carcinoma cells. Cancer Lett. 325:207–213. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Yue P, Zhang X, Paladino D, Sengupta B, Ahmad S, Holloway RW, Ingersoll SB and Turkson J: Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells. Oncogene. 31:2309–2322. 2012. View Article : Google Scholar

20 

Jung JE, Lee HG, Cho IH, Chung DH, Yoon SH, Yang YM, Lee JW, Choi S, Park JW, Ye SK, et al: STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 19:1296–1298. 2005.PubMed/NCBI

21 

Pawlus MR, Wang L and Hu CJ: STAT3 and HIF1α cooperatively activate HIF1 target genes in MDA-MB-231 and RCC4 cells. Oncogene. 33:1670–1679. 2014. View Article : Google Scholar

22 

Xu Q, Briggs J, Park S, Niu G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza GL, et al: Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene. 24:5552–5560. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Ardyanto TD, Osaki M, Tokuyasu N, Nagahama Y and Ito H: CoCl2-induced HIF-1alpha expression correlates with proliferation and apoptosis in MKN-1 cells: A possible role for the PI3K/Akt pathway. Int J Oncol. 29:549–555. 2006.PubMed/NCBI

24 

Yang G, Huang C, Cao J, Huang KJ, Jiang T and Qiu ZJ: Lentivirus-mediated shRNA interference targeting STAT3 inhibits human pancreatic cancer cell invasion. World J Gastroenterol. 15:3757–3766. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Lakka SS, Rajan M, Gondi C, Yanamandra N, Chandrasekar N, Jasti SL, Adachi Y, Siddique K, Gujrati M, Olivero W, et al: Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene. 21:8011–8019. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Santel A, Aleku M, Röder N, Möpert K, Durieux B, Janke O, Keil O, Endruschat J, Dames S, Lange C, et al: Atu027 prevents pulmonary metastasis in experimental and spontaneous mouse metastasis models. Clin Cancer Res. 16:5469–5480. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Yang HB, Yang X, Cao J, Li S, Liu YN, Suo ZW, Cui HB, Guo Z and Hu XD: cAMP-dependent protein kinase activated Fyn in spinal dorsal horn to regulate NMDA receptor function during inflammatory pain. J Neurochem. 116:93–104. 2011. View Article : Google Scholar

28 

Cannito S, Novo E, Compagnone A, Valfrè di Bonzo L, Busletta C, Zamara E, Paternostro C, Povero D, Bandino A, Bozzo F, et al: Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis. 29:2267–2278. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X, et al: Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor-1α in hepatocellular carcinoma. BMC Cancer. 13:1082013. View Article : Google Scholar

30 

Matsuyama T, Nakanishi K, Hayashi T, Yoshizumi Y, Aiko S, Sugiura Y, Tanimoto T, Uenoyama M, Ozeki Y and Maehara T: Expression of hypoxia-inducible factor-1alpha in esophageal squamous cell carcinoma. Cancer Sci. 96:176–182. 2005. View Article : Google Scholar : PubMed/NCBI

31 

You Z, Xu D, Ji J, Guo W, Zhu W and He J: JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma. Clin Transl Oncol. 14:143–149. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Yang Y, Pan X, Lei W, Wang J, Shi J, Li F and Song J: Regulation of transforming growth factor-beta 1-induced apoptosis and epithelial-to-mesenchymal transition by protein kinase A and signal transducers and activators of transcription 3. Cancer Res. 66:8617–8624. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM and Hall BM: Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene. 28:2940–2947. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Niu G, Briggs J, Deng J, Ma Y, Lee H, Kortylewski M, Kujawski M, Kay H, Cress WD, Jove R, et al: Signal transducer and activator of transcription 3 is required for hypoxia-inducible factor-1alpha RNA expression in both tumor cells and tumor-associated myeloid cells. Mol Cancer Res. 6:1099–1105. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cui Y, Li Y, Li J, Zhang H, Wang F, Bai X and Li S: STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer. Oncol Rep 36: 108-116, 2016.
APA
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., & Li, S. (2016). STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer. Oncology Reports, 36, 108-116. https://doi.org/10.3892/or.2016.4822
MLA
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., Li, S."STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer". Oncology Reports 36.1 (2016): 108-116.
Chicago
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., Li, S."STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer". Oncology Reports 36, no. 1 (2016): 108-116. https://doi.org/10.3892/or.2016.4822
Copy and paste a formatted citation
x
Spandidos Publications style
Cui Y, Li Y, Li J, Zhang H, Wang F, Bai X and Li S: STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer. Oncol Rep 36: 108-116, 2016.
APA
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., & Li, S. (2016). STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer. Oncology Reports, 36, 108-116. https://doi.org/10.3892/or.2016.4822
MLA
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., Li, S."STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer". Oncology Reports 36.1 (2016): 108-116.
Chicago
Cui, Y., Li, Y., Li, J., Zhang, H., Wang, F., Bai, X., Li, S."STAT3 regulates hypoxia-induced epithelial mesenchymal transition in oesophageal squamous cell cancer". Oncology Reports 36, no. 1 (2016): 108-116. https://doi.org/10.3892/or.2016.4822
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