PMID- 25426556 OWN - NLM STAT- MEDLINE DCOM- 20160405 LR - 20231213 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 12 DP - 2015 Apr 30 TI - Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways. PG - 10116-33 AB - Hepatocellular carcinoma (HCC) progresses rapidly and is frequently associated with vascular invasion, metastasis, recurrence, and poor prognosis. The expression of connexin32 (Cx32) is frequently downregulated in HCC tissues. In this study, the role of Cx32 in HCC metastasis and proliferation was investigated. The reduction of Cx32 in HCC tissues was significantly associated with increased vascular invasion, increased tumor size, and poor survival. In vitro assays revealed that Cx32 not only suppressed the invasion and migration of HCC cells, but also repressed HCC cell proliferation. Subsequent investigations revealed that Cx32 directly enhanced the acetylation and transcriptional activity of p53, thus upregulating the expression of the tumor metastasis suppressor protein KAI1/CD82, which is a p53 target gene. Additionally, Cx32 negatively regulated the phosphorylation of Akt and the expression of the cell cycle regulation protein cyclin D1, thereby inhibiting the proliferation of HCC cells. Our in vivo nude mice model further confirmed that Cx32 is able to suppress HCC tumor growth and metastasis in nude mice. Our results imply that Cx32 downregulation contributes to the proliferation and metastasis of HCC, and the restoration of Cx32 expression may be a promising strategy for HCC therapy. FAU - Zhao, Bixing AU - Zhao B AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Zhao, Wenxiu AU - Zhao W AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Wang, Yu AU - Wang Y AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Xu, Yaping AU - Xu Y AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Xu, Jianfeng AU - Xu J AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Tang, Kai AU - Tang K AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Zhang, Sheng AU - Zhang S AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Yin, Zhenyu AU - Yin Z AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. FAU - Wu, Qiao AU - Wu Q AD - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. FAU - Wang, Xiaomin AU - Wang X AD - Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital, Xiamen, Fujian, China. AD - Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Connexins) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Carcinoma, Hepatocellular/genetics/metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Connexins/genetics/*metabolism MH - Female MH - HEK293 Cells MH - Hep G2 Cells MH - Humans MH - Liver Neoplasms/genetics/metabolism/*pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Middle Aged MH - Neoplasm Metastasis MH - Proto-Oncogene Proteins c-akt/genetics/*metabolism MH - Signal Transduction MH - Gap Junction beta-1 Protein PMC - PMC4496344 OTO - NOTNLM OT - connexin32 OT - hepatocellular carcinoma OT - invasion OT - migration OT - p53 COIS- Conflicts of interest The authors disclose no potential conflicts of interest. EDAT- 2014/11/27 06:00 MHDA- 2016/04/06 06:00 PMCR- 2015/04/30 CRDT- 2014/11/27 06:00 PHST- 2014/08/13 00:00 [received] PHST- 2014/11/02 00:00 [accepted] PHST- 2014/11/27 06:00 [entrez] PHST- 2014/11/27 06:00 [pubmed] PHST- 2016/04/06 06:00 [medline] PHST- 2015/04/30 00:00 [pmc-release] AID - 2687 [pii] AID - 10.18632/oncotarget.2687 [doi] PST - ppublish SO - Oncotarget. 2015 Apr 30;6(12):10116-33. doi: 10.18632/oncotarget.2687.