Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways.
Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways.
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Connexin32 通过 p53 和 Akt 通路调节肝癌细胞转移和增殖
DOI：
10.18632/oncotarget.2687
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发表时间：
2015-04-30
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Zhao B;Zhao W;Wang Y;Xu Y;Xu J;Tang K;Zhang S;Yin Z;Wu Q;Wang X
肝细胞癌（HCC）进展迅速，常伴有血管浸润、转移、复发和预后不良。Cx 32在肝癌组织中表达下调。在这项研究中，Cx 32在肝癌转移和增殖的作用进行了研究。Cx 32在HCC组织中的减少与血管浸润增加、肿瘤大小增加和生存率降低显著相关。体外实验表明，Cx 32不仅抑制肝癌细胞的侵袭和迁移，而且抑制肝癌细胞的增殖。随后的研究表明，Cx 32直接增强p53的乙酰化和转录活性，从而上调肿瘤转移抑制蛋白KAI 1/CD 82的表达，这是一个p53的靶基因。另外，Cx 32还能负性调节Akt的磷酸化和细胞周期调节蛋白cyclin D1的表达，从而抑制肝癌细胞的增殖。我们的体内裸鼠模型进一步证实了Cx 32能够抑制裸鼠中HCC肿瘤的生长和转移。我们的研究结果表明，Cx 32的下调有助于肝癌的增殖和转移，和Cx 32的表达的恢复可能是一个有前途的策略，肝癌的治疗。
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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