Connexin-43 (Cx43) is the most characterized gap junction protein, primarily involved in the Gap Junctional Intercellular Communication (GJIC) between adjacent cells to facilitate molecule exchange and the formation of a signaling network. It is increasingly evident that the importance of Cx43 is not only limited to its GJIC function, but rather includes its role in connecting the intracellular and extracellular environment by forming membrane hemichannels, as well as its intracellular signaling function mediated by its C-terminal tail (Cx43-CT). Notably, Cx43 has been implicated in a variety of cancers, with earlier notions suggesting a tumor-suppressor function, whereas new studies shed light on its pro-tumorigenic role. Moreover, apart from GJIC-based activities, the relevance of the non-canonical functions of Cx43 in tumor progression is being actively studied. This review provides an analysis of the current research on the pro-tumorigenic roles of Cx43, with a focus on Cx43-CT interactions and the function of hemichannels in cancer progression. A better understanding of the multifaceted functions of Cx43 in cancer biology could foster its recognition as a pivotal target for the development of innovative therapeutic strategies.
连接蛋白-43（Cx43）是目前研究最为深入的间隙连接蛋白，主要通过介导相邻细胞间的间隙连接通讯（GJIC）促进分子交换并形成信号网络。越来越多的证据表明，Cx43的重要性不仅限于其GJIC功能，还包括通过形成膜半通道连接细胞内外的功能，以及由其C末端（Cx43-CT）介导的细胞内信号传导功能。值得注意的是，Cx43与多种癌症的发生发展密切相关，早期研究认为其具有抑癌作用，而新近研究则揭示了其促癌功能。此外，除基于GJIC的功能外，Cx43非经典功能在肿瘤进展中的相关性也正被积极研究。本文综述了当前关于Cx43促癌作用的研究进展，重点关注Cx43-CT相互作用及半通道在癌症进展中的功能。深入理解Cx43在癌症生物学中的多重功能，将有助于确立其作为创新治疗策略开发关键靶点的重要地位。
肿瘤(癌症)患者之家