PMID- 28901517
OWN - NLM
STAT- MEDLINE
DCOM- 20180604
LR  - 20231213
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 5
DP  - 2017 Nov
TI  - Cx32 inhibits TNFalpha-induced extrinsic apoptosis with and without EGFR suppression.
PG  - 2885-2892
LID - 10.3892/or.2017.5950 [doi]
AB  - Tumor necrosis factor alpha (TNFalpha) 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 TNFalpha + 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, 18alpha-glycyrrhetinic acid (18alpha-GA), a 
      gap junction intracellular communication (GJIC) inhibitor, was used. Our results 
      showed that Cx32 could inhibit apoptosis induced by TNFalpha + 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 TNFalpha treatment. After 
      knocking down Cx32 in C-33A cells, the expression levels of survivin and TNFalpha 
      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.
FAU - Lai, Yongchang
AU  - Lai Y
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Tao, Liang
AU  - Tao L
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Zhao, Yifan
AU  - Zhao Y
AD  - Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong 510120, P.R. China.
FAU - Zhang, Xiaomin
AU  - Zhang X
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Sun, Xingjuan
AU  - Sun X
AD  - Traditional Chinese Medicine Hospital of Guangdong, Guangzhou, Guangdong 510120, 
      P.R. China.
FAU - Wang, Qin
AU  - Wang Q
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Xu, Chengfang
AU  - Xu C
AD  - Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun 
      Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170907
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Connexins)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (Survivin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 41UD74L59M (Afatinib)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Afatinib
MH  - Apoptosis
MH  - Connexins/genetics/*metabolism
MH  - Cycloheximide/*pharmacology
MH  - Doxycycline/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - HeLa Cells
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/metabolism
MH  - Phosphorylation
MH  - Quinazolines/*pharmacology
MH  - Survivin
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Uterine Cervical Neoplasms/genetics/*metabolism
MH  - Gap Junction beta-1 Protein
EDAT- 2017/09/14 06:00
MHDA- 2018/06/05 06:00
CRDT- 2017/09/14 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/07/21 00:00 [accepted]
PHST- 2017/09/14 06:00 [pubmed]
PHST- 2018/06/05 06:00 [medline]
PHST- 2017/09/14 06:00 [entrez]
AID - 10.3892/or.2017.5950 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Nov;38(5):2885-2892. doi: 10.3892/or.2017.5950. Epub 2017 Sep 7.