Research Papers:

Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways

Bixing Zhao _, Wenxiu Zhao, Yu Wang, Yaping Xu, Jianfeng Xu, Kai Tang, Sheng Zhang, Zhenyu Yin, Qiao Wu and Xiaomin Wang

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Oncotarget. 2015; 6:10116-10133. https://doi.org/10.18632/oncotarget.2687

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Bixing Zhao1,2, Wenxiu Zhao1,2, Yu Wang1,2, Yaping Xu1,2, Jianfeng Xu1,2, Kai Tang1,2, Sheng Zhang1,2, Zhenyu Yin1,2, Qiao Wu3, Xiaomin Wang1,2

1Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University. Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated Zhongshan Hospital

2Research Institute of Digestive Disease, Xiamen University, Xiamen, Fujian, China

3State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China

Correspondence to:

Xiaomin Wang, e-mail: [email protected]

Wenxiu Zhao, e-mail: [email protected]

Keywords: connexin32, p53, hepatocellular carcinoma, invasion, migration

Received: August 13, 2014     Accepted: November 02, 2014     Published: November 27, 2014


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.

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