title: STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1.
abstract: The transcription factor signal transducer and activator of transcription 3 (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis process and molecular mechanisms. We showed that hyperactivated STAT3 in esophageal carcinogenesis tissues correlated with the overexpression of octamer transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1 expression levels affected the proliferation and colony formation of Eca-109 esophageal squamous cell carcinoma cells by altering Erk and Akt activation. Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3 inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct-1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is sufficient for carcinogenesis. We further confirmed the colocalization of STAT3 and Oct-1 in the nucleus and found that STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter. Activated STAT3 also upregulated many genes associated with Oct-1. Together, our results indicate that STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell proliferation and apoptosis in conjunction with Oct-1.
authors.affiliation: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Shaojun
authors.initials: S
authors.lastname: Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wang
authors.forename: Anmei
authors.initials: A
authors.lastname: Deng
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D027702:Organic Cation Transporter 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D047368:Tumor Burden
chemical_list: D027702:Organic Cation Transporter 1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9