Connexin亚细胞定位与肿瘤发生发展关系的研究进展

Research progresses on correlation between connexin subcellular distribution and tumorigenesis and development

缝隙连接蛋白(connexin,Cx)是一个多基因编码的跨膜蛋白家族,能够在细胞膜上组成缝隙连接通道(gap junction,GJ)和半通道(hemichannel,HC),介导细胞之间、细胞质与细胞外环境之间的通讯功能,或在细胞质中通过羧基端与其他蛋白分子相互作用,参与肿瘤细胞增殖、凋亡、坏死、侵袭、转移、耐药和干细胞特性等过程。Cx在许多肿瘤细胞中常出现细胞质或细胞核等异常亚细胞定位并参与肿瘤的发生发展。翻译后修饰(包括磷酸化、泛素化、乙酰化等)是影响Cx亚细胞定位的重要因素。该文从Cx的分类、功能及其亚细胞定位与肿瘤发生发展的关系以及翻译后修饰对Cx亚细胞定位的重要影响进行综述,以期为Cx作为抗肿瘤药物治疗的潜在靶点提供新的思路。

Connexin(Cx),a multigene-encoded transmembrane protein family,forms either gap junctions(GJ)or hemichannels(HC)to mediate intercellular communication in plasma membrane between adjacent cells or interacts with proteins by its carboxyl terminal in the cytoplasm to participate in the process of tumor cell proliferation,apoptosis,necrosis,invasion,metastasis,drug resistance and stem cell characteristics.However,mislocalization of Cx in cytoplasm or nucleus often occurs in many tumors,and involved in the occurrence and development of tumors.Subcellular localization of Cx is affected by post-translational modifications,including phosphorylation,ubiquitination,and acetylation.In this paper the classification and function of Cx,the relationship between subcellular localization of Cx and tumorigenesis and the regulation of post-translational modification on Cx are reviewed in order to provide new ideas for the study of Cx as a potential target for cancer therapy.