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.

Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

“…Moreover, STAT3 phosphorylation and translocation to the nucleus promote GBM migration [48]. Previous reports have indicated that STAT3 increases HIF-1α protein stability and interacts with HIF-1α target gene promoters [62]. Other reports have also shown that activation of STAT3 is involved in the modulation of expression of pH-regulating proteins, CA9 and MCT4 [63].…”

Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF‐1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue

“…With the development of biotechnology, the changes for some functional proteins have been revealed in CRC tissues [2–4]. Hypoxia is prognostically important in cancer therapy and it has a deep impact on malignant development of various cancers [5, 6]. HIF-1 (hypoxia inducible factor-1), a kind of hydrocarbon nuclear translators, plays an important role in oxygen homeostasis [7] and consists of two subunits, HIF-1 alpha and HIF-1 beta.…”

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

“…TRPC1 is a regulator of hypoxia-induced EGFR and STAT3 activation EGFR and STAT3 signalling are two key hypoxia-associated signalling pathways (Selvendiran et al, 2009;Pawlus et al, 2014;Peng et al, 2006) that also have important roles in EMT induced by hypoxia (Cui et al, 2016;Misra et al, 2012) and EGF (Lo et al, 2007), although their potential regulation by TRPC1 is unknown. We assessed EGFR at Y1173 (an important site of EGFR autophosphorylation; Kondratov et al, 2010) and STAT3 phosphorylation at Y705 in MDA-MB-468 cells under hypoxic conditions for 6, 24 and 48 h. Phosphorylation of EGFR was significantly enhanced after 24 and 48 h of hypoxia, with no significant concomitant change in total EGFR protein ( Fig.…”