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

Cui,Yao; Li,Yun-Yun; Li,Jian; Zhang,Hong-Yan; Wang,Feng; Bai,Xue; Li,Shan-Shan

doi:10.3892/or.2016.4822

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
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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
Published online on: May 19, 2016 https://doi.org/10.3892/or.2016.4822
Pages: 108-116
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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