title: Exposure to TNF‑α combined with TGF‑β induces carcinogenesis in vitro via NF-κB/Twist axis.
abstract: Persistent human papilloma virus (HPV) infection induces chronic inflammation resulting in human cervical cancer. However, the mechanisms underlying carcinogenesis via chronic inflammation remain largely unclear. We investigated the role of pro-inflammatory factors in epithelial-mesenchymal transition (EMT) and cancer stem cell-like (CSCL) characteristics of HeLa cells exposed to TNF‑α with or without TGF‑β. We then determined the role of NF-κB/Twist signal axis in the pathogenesis of cervical cancer. We found that HeLa cells exposed to TNF‑α following chronic treatment with TGF‑β exhibited EMT, self-renewal and high mobility. Knockdown of NF-κBp65 inhibited NF-κB and Twist1 expression, and EMT and CSCL properties of HeLa cells following co-treatment with TNF‑α and TGF‑β. Conversely, overexpression of NF-κBp65 potentiated the above effects. However, knockdown or overexpression of Twist1 had no effect on NF-κBp65 expression, but inhibited or promoted EMT and CSCL features. Notably, overexpression of Twist1 rescued NF-κBp65 knockdown. Our results demonstrate the role of NF-κB/Twist signaling axis in which HeLa cells treated with TNF‑α following chronic exposure to TGF‑β induce EMT and CSCL properties. The NF-κB/Twist signal axis may represent an effective therapeutic target in cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Weilei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051879:Twist-Related Protein 1