间隙连接是由连接蛋白 (Cxs) 组成的基于膜的通道，可通过其半通道促进相邻细胞之间以及细胞与细胞外空间之间的直接通讯。正常人乳房表达各种 Cxs 家族蛋白，例如 Cx43、Cx30、Cx32、Cx46 和 Cx26，这对于组织的正常发育和功能至关重要。这些蛋白质在乳腺癌的发生、进展和治疗反应中发挥着重要作用。在原发性肿瘤中，Cx43 和 Cx26 经常减少且细胞质错误定位，而转移性病变则显示这些和其他 Cxs 的上调。尽管现有研究主要支持 Cxs 通过通道依赖性和独立功能在原发性癌中发挥肿瘤抑制作用，但关于它们参与转移过程的争议仍然存在。本综述旨在提供有关人类乳腺癌 Cxs 的最新观点，特别关注由于这种疾病的异质性而产生的内在亚型。此外，该手稿还将探讨 Cxs 在乳腺肿瘤背景和肿瘤微环境中的免疫相互作用和新型细胞间通讯（例如隧道纳米管和细胞外囊泡）中的作用。最近的研究结果表明，Cxs 具有作为减轻转移和耐药性的治疗靶点的潜力。此外，它们可以作为癌症预后的新型生物标志物，为未来的研究和临床应用提供有前景的途径。版权所有 © 2024。由 Elsevier B.V. 出版。

Gap junctions, membrane-based channels comprised of connexin proteins (Cxs), facilitate direct communication among neighbouring cells and between cells and the extracellular space through their hemichannels. The normal human breast expresses various Cxs family proteins, such as Cx43, Cx30, Cx32, Cx46, and Cx26, crucial for proper tissue development and function. These proteins play a significant role in breast cancer development, progression, and therapy response. In primary tumours, there is often a reduction and cytoplasmic mislocalization of Cx43 and Cx26, while metastatic lesions show an upregulation of these and other Cxs. Although existing research predominantly supports the tumour-suppressing role of Cxs in primary carcinomas through channel-dependent and independent functions, controversies persist regarding their involvement in the metastatic process. This review aims to provide an updated perspective on Cxs in human breast cancer, with a specific focus on intrinsic subtypes due to the heterogeneous nature of this disease. Additionally, the manuscript will explore the role of Cxs in immune interactions and novel forms of intercellular communication, such as tunneling nanotubes and extracellular vesicles, within the breast tumour context and tumour microenvironment. Recent findings suggest that Cxs hold potential as therapeutic targets for mitigating metastasis and drug resistance. Furthermore, they may serve as novel biomarkers for cancer prognosis, offering promising avenues for future research and clinical applications.Copyright © 2024. Published by Elsevier B.V.