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Article

Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression

  • Authors:
    • Yongchang Lai
    • Liang Tao
    • Yifan Zhao
    • Xiaomin Zhang
    • Xingjuan Sun
    • Qin Wang
    • Chengfang Xu
  • View Affiliations / Copyright

    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, Traditional Chinese Medicine Hospital of Guangdong, Guangzhou, Guangdong 510120, P.R. China, Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
  • Pages: 2885-2892
    |
    Published online on: September 7, 2017
       https://doi.org/10.3892/or.2017.5950
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Abstract

Tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand (TRAIL) can trigger the extrinsic apoptosis pathway. Our previous study indicated that connexin32 (Cx32) inhibited streptonigrin-induced intrinsic apoptosis via the epidermal growth factor receptor (EGFR) pathway. However, whether Cx32 can exert effects on the extrinsic apoptosis pathway through EGFR signaling remains unclear. In the present study, we investigated the role of Cx32 in extrinsic apoptosis induced by treatment with TNFα + cycloheximide (CHX) or afatinib in human cervical cancer (CaCx) cells. In stable inducible Cx32-transfected HeLa cells (HeLa-Cx32), Cx32 expression was induced by treatment with doxycycline (Dox). Furthermore, C-33A cells, which natively express high levels of Cx32, were used as a cell model for knockdown of Cx32 with siRNA. To determine the non-junctional function of Cx32 in apoptosis, 18α-glycyrrhetinic acid (18α-GA), a gap junction intracellular communication (GJIC) inhibitor, was used. Our results showed that Cx32 could inhibit apoptosis induced by TNFα + afatinib with or without the GJIC inhibitor. In clinical cervical tissue samples, we found that the expression of survivin was markedly higher in CaCx than in normal cervix tissue, which was in accordance with the expression of Cx32 in our previous study. In HeLa-Cx32 cells, we also found that Cx32 upregulated the expression of Cox-2. In addition, Cx32 upregulated EGFR expression in low-density culture (lacking GJ formation). Cx32 could also promote the expression of EGFR, phospho-STAT3 and phospho-ERK in HeLa-Cx32 cells following TNFα treatment. After knocking down Cx32 in C-33A cells, the expression levels of survivin and TNFα were downregulated. The present study verifies that Cx32 exerts an inhibitory effect on extrinsic apoptosis in CaCx cells, and suggests that Cx32 may regulate the progression and micro-environment of CaCx cells.
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Copy and paste a formatted citation
Spandidos Publications style
Lai Y, Tao L, Zhao Y, Zhang X, Sun X, Wang Q and Xu C: Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression. Oncol Rep 38: 2885-2892, 2017.
APA
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., & Xu, C. (2017). Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression. Oncology Reports, 38, 2885-2892. https://doi.org/10.3892/or.2017.5950
MLA
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., Xu, C."Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression". Oncology Reports 38.5 (2017): 2885-2892.
Chicago
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., Xu, C."Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression". Oncology Reports 38, no. 5 (2017): 2885-2892. https://doi.org/10.3892/or.2017.5950
Copy and paste a formatted citation
x
Spandidos Publications style
Lai Y, Tao L, Zhao Y, Zhang X, Sun X, Wang Q and Xu C: Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression. Oncol Rep 38: 2885-2892, 2017.
APA
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., & Xu, C. (2017). Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression. Oncology Reports, 38, 2885-2892. https://doi.org/10.3892/or.2017.5950
MLA
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., Xu, C."Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression". Oncology Reports 38.5 (2017): 2885-2892.
Chicago
Lai, Y., Tao, L., Zhao, Y., Zhang, X., Sun, X., Wang, Q., Xu, C."Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression". Oncology Reports 38, no. 5 (2017): 2885-2892. https://doi.org/10.3892/or.2017.5950
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