Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Cancer Lett. 2019 Feb 1;442:439-444. doi: 10.1016/j.canlet.2018.10.043. Epub 2018 Nov 22.
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.
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，负责在相邻细胞或细胞与其细胞外环境之间传递生物活性分子、代谢物和盐。在过去的几年中，异常的连接蛋白 43（Cx43）表达与癌症复发、转移扩散和预后不良有关。在这里，我们提供了间隙连接的一般结构和功能概述，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新潜在方法。Cx43 通道对小分子和大分子的通透性使它们成为将药物直接递送到细胞质的极具吸引力的靶标。过表达 Cx43 的癌细胞可能更通透，对化疗药物更敏感。由于 Cx43 可以作为肿瘤抑制因子或癌基因发挥作用，因此需要进行生物标志物分析和更好地了解 Cx43 如何在上下文中调节癌症表型，以开发临床可行的基于 Cx43 的治疗方法。
