title: 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.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of General Surgery, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University and Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003035:Cobalt; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014746:Vimentin; D003035:Cobalt; C018021:cobaltous chloride