Exposure to TNF‑α combined with TGF‑β induces carcinogenesis in vitro via NF-κB/Twist axis

Dong,Weilei; Sun,Shuwen; Cao,Xiaocheng; Cui,Yinghong; Chen,A.; Li,Xiang; Zhang,Jiansong; Cao,Jianguo; Wang,Yifeng

doi:10.3892/or.2017.5369

Exposure to TNF‑α combined with TGF‑β induces carcinogenesis in vitro via NF-κB/Twist axis

Authors:
- Weilei Dong
- Shuwen Sun
- Xiaocheng Cao
- Yinghong Cui
- A. Chen
- Xiang Li
- Jiansong Zhang
- Jianguo Cao
- Yifeng Wang
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Affiliations: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China
Published online on: January 16, 2017 https://doi.org/10.3892/or.2017.5369
Pages: 1873-1882

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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.

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