Insights into the role of connexins and specialized intercellular communication pathways in breast cancer: Mechanisms and applications

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-08-16 DOI:10.1016/j.bbcan.2024.189173
Marina Rodríguez-Candela Mateos , Paula Carpintero-Fernández , Paz Santiago Freijanes , Joaquin Mosquera , Benigno Acea Nebril , María D. Mayán
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Abstract

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.

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洞察附件蛋白和专门的细胞间通讯途径在乳腺癌中的作用:机制与应用
间隙连接是由连接蛋白(Cxs)组成的膜基通道,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交流。正常人的乳房表达多种 Cxs 家族蛋白,如 Cx43、Cx30、Cx32、Cx46 和 Cx26,它们对组织的正常发育和功能至关重要。这些蛋白在乳腺癌的发生、发展和治疗反应中起着重要作用。在原发性肿瘤中,Cx43 和 Cx26 通常会减少并在细胞质中错误定位,而转移性病灶则显示出这些和其他 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症中发挥抑制肿瘤的作用,但关于它们在转移过程中的参与仍存在争议。本综述旨在提供有关人类乳腺癌中 Cxs 的最新观点,由于乳腺癌的异质性,本综述特别关注内在亚型。此外,文稿还将探讨 Cxs 在乳腺肿瘤和肿瘤微环境中的免疫相互作用和新型细胞间通信形式(如隧道纳米管和细胞外囊泡)中的作用。最新研究结果表明,Cxs 有可能成为减轻转移和耐药性的治疗靶点。此外,它们还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了广阔的前景。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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