Cx32 suppresses extrinsic apoptosis in human cervical cancer cells via the NF‑κB signalling pathway

Lai,Yongchang; Fan,Lixia; Zhao,Yifan; Ge,Hui; Feng,Xue; Wang,Qin; Zhang,Xiaomin; Peng,Yuexia; Wang,Xiyan; Tao,Liang

doi:10.3892/ijo.2017.4106

Cx32 suppresses extrinsic apoptosis in human cervical cancer cells via the NF‑κB signalling pathway

Authors:
- Yongchang Lai
- Lixia Fan
- Yifan Zhao
- Hui Ge
- Xue Feng
- Qin Wang
- Xiaomin Zhang
- Yuexia Peng
- Xiyan Wang
- Liang Tao
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Affiliations: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China, Tumor Research Institute, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang 830000, P.R. China
Published online on: August 29, 2017 https://doi.org/10.3892/ijo.2017.4106
Pages: 1159-1168

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Abstract

Tumour necrosis factor α (TNFα) and TNF‑related apoptosis inducing ligand (TRAIL) usually trigger either survival or apoptosis signals in various cell types, and nuclear factor κB (NF‑κB) is a key factor that regulates their biological effects. Connexin 32 (Cx32) is a gap junction (GJ) protein that plays vital roles in tumourigenesis and tumour progression. Our previous study explored abnormal Cx32 expression in para‑nuclear areas, exacerbated prognostic parameters and suppressed streptonigrin/cisplatin-induced apoptosis in human cervical cancer (CaCx) cells. In this study, we investigated the role of Cx32 in the extrinsic apoptosis pathway of CaCx cells. In transgenic HeLa cells and C-33A cells, Cx32 expression was manipulated using doxycycline or Cx32 siRNA. GJ inhibitors or low density culturing was used to change the status of gap junction intracellular communication (GJIC). We found that apoptosis induced by TNFα and TRAIL was suppressed by Cx32 expression despite the presence or absense of GJIC. We also found that Cx32 upregulated the expression of nuclear NF‑κB and its downstream targets c-IAP1, MMP‑2, and MMP‑9 in HeLa‑Cx32 and C-33A cells. Following our previous study design, our clinical data showed that NF‑κB and MMP‑2 levels increased in human CaCx specimens with high Cx32 expression compared to levels in para‑carcinoma of cervical specimens. SC75741 and JSH-23, NF‑кB signalling pathway inhibitors, inhibited the anti-apoptotic effects of Cx32. In conclusion, Cx32 suppressed TNFα /TRAIL-induced extrinsic apoptosis by upregulating the NF‑κB signalling pathway. This study demonstrates a novel mechanism for Cx32's anti-apoptotic effect and provides a reasonable explanation for the pro-tumour effect of Cx32 in human CaCx cells.

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