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

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.