Connexin 43 (Cx43) in cancer: Implications for therapeutic approaches via gap junctions
Connexin 43 (Cx43) in cancer: Implications for therapeutic approaches via gap junctions
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DOI：
10.1016/j.canlet.2018.10.043
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发表时间：
2019-02-01
期刊：
影响因子：
9.7
通讯作者：
Nguyen, Juliane
中科院分区：
文献类型：
--
作者：
Bonacquisti, Emily E.;Nguyen, Juliane
间隙连接是人体所有细胞中发现的膜通道，对细胞生理学至关重要。间隙连接由连接蛋白形成，负责生物活性分子、代谢物和盐在相邻细胞或细胞与其细胞外环境之间的转移。在过去的几年中，异常的连接蛋白 43 (Cx43) 表达与癌症复发、转移扩散和较差的生存率有关。在这里，我们概述了间隙连接的一般结构和功能，并回顾了它们在不同癌症类型中的作用。我们讨论了针对 Cx43 的新治疗方法以及利用间隙连接转移进行药物输送和抗癌治疗的潜在新方法。 Cx43 通道对小分子和大分子的渗透性使其成为将药物直接输送到细胞质中的极具吸引力的靶标。过度表达 Cx43 的癌细胞可能更具渗透性，对化疗药物更敏感。由于 Cx43 可以充当肿瘤抑制基因或癌基因，因此需要进行生物标志物分析并更好地了解 Cx43 如何介导癌症表型，以开发临床上可行的基于 Cx43 的疗法。
Gap junctions are membrane channels found in all cells of the human body that are essential to cellular physiology. Gap junctions are formed from connexin proteins and are responsible for transfer of biologically active molecules, metabolites, and salts between neighboring cells or cells and their extracellular environment. Over the last few years, aberrant connexin 43 (Cx43) expression has been associated with cancer recurrence, metastatic spread, and poor survival. Here we provide an overview of the general structure and function of gap junctions and review their roles in different cancer types. We discuss new therapeutic approaches targeting Cx43 and potential new ways of exploiting gap junction transfer for drug delivery and anti-cancer treatment. The permeability of Cx43 channels to small molecules and macromolecules makes them highly attractive targets for delivering drugs directly into the cytoplasm. Cancer cells overexpressing Cx43 may be more permeable and sensitive to chemotherapeutics. Because Cx43 can either act as a tumor suppressor or oncogene, biomarker analysis and a better understanding of how Cx43 contextually mediates cancer phenotypes will be required to develop clinically viable Cx43-based therapies.