title: Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma.
abstract: Epithelial-mesenchymal transition (EMT) is an important process in the invasion and metastasis of human cervical carcinoma. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown as an EMT inducer in multiple carcinomas. However, whether the EMT program can be induced by IL-6 and the mechanisms underlying the IL-6-induced EMT in human cervical carcinoma remain to be determined. In this study, we show that IL-6 receptor (IL-6R) and signal transducer and activator of transcription 3 (Stat3) were highly expressed in human cervical squamous cell carcinoma (CSCC) tissues, and the expression of EMT markers was reversed in well-differentiated and poorly-differentiated human CSCC. Additional experiments showed that IL-6 exposure in cervical carcinoma cell lines induced IL-6R and Stat3 expression, markedly promoted cell growth, and altered cell morphology. The treatment of cervical carcinoma cell lines with IL-6 resulted in downregulation of E-Cadherin and upregulation of Vimentin. Importantly, knockdown of Stat3 significantly reversed the IL-6-induced EMT program, suggesting that Stat3 is necessary for IL-6-induced EMT in the progression of human cervical carcinoma. Moreover, Slug, a member of the Snail family of EMT regulators, was observed to be associated with the expression of Stat3. We concluded that IL-6 plays an important role through Stat3 in the EMT induction and can be a potential therapeutic target and biomarker for human cervical carcinoma.
authors.affiliation: Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Miao
authors.affiliation: Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, P.R. China.
authors.forename: Li-Jiang
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015820:Cadherins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014746:Vimentin; D003474:Curcumin