Cx32 inhibits TNF α-induced extrinsic apoptosis with and without EGFR suppression.

Cx32 inhibits TNFα-induced extrinsic apoptosis with and without EGFR suppression. Oncol Rep. 2017 Sep 07;: Authors: Lai Y, Tao L, Zhao Y, Zhang X, Sun X, Wang Q, Xu C 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 a...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research