Department of Biochemistry and Molecular Biology, LSUHSC, School of Medicine, New Orleans, LA, USA.
Department of Medical Genetics, Tehran University of Medical Sciences, School of Medicine, Tehran, Iran.
Oncogene. 2021 Feb;40(6):1043-1063. doi: 10.1038/s41388-020-01588-2. Epub 2021 Jan 8.
Integrins are cell adhesion receptors, which are typically transmembrane glycoproteins that connect to the extracellular matrix (ECM). The function of integrins regulated by biochemical events within the cells. Understanding the mechanisms of cell growth by integrins is important in elucidating their effects on tumor progression. One of the major events in integrin signaling is integrin binding to extracellular ligands. Another event is distant signaling that gathers chemical signals from outside of the cell and transmit the signals upon cell adhesion to the inside of the cell. In normal breast tissue, integrins function as checkpoints to monitor effects on cell proliferation, while in cancer tissue these functions altered. The combination of tumor microenvironment and its associated components determines the cell fate. Hypoxia can increase the expression of several integrins. The exosomal integrins promote the growth of metastatic cells. Expression of certain integrins is associated with increased metastasis and decreased prognosis in cancers. In addition, integrin-binding proteins promote invasion and metastasis in breast cancer. Targeting specific integrins and integrin-binding proteins may provide new therapeutic approaches for breast cancer therapies. This review will examine the current knowledge of integrins' role in breast cancer.
整合素是细胞黏附受体,通常是细胞外基质(ECM)连接的跨膜糖蛋白。整合素的功能受细胞内生化事件调节。了解整合素对细胞生长的作用机制对于阐明其对肿瘤进展的影响很重要。整合素信号转导的主要事件之一是整合素与细胞外配体结合。另一个事件是远程信号转导,它从细胞外部收集化学信号,并在细胞黏附时将信号传递到细胞内部。在正常乳腺组织中,整合素作为检查点发挥作用,以监测对细胞增殖的影响,而在癌症组织中,这些功能发生了改变。肿瘤微环境及其相关成分的结合决定了细胞命运。缺氧可增加几种整合素的表达。外泌体整合素促进转移性细胞的生长。某些整合素的表达与癌症中转移增加和预后降低有关。此外,整合素结合蛋白促进乳腺癌的侵袭和转移。针对特定的整合素和整合素结合蛋白可能为乳腺癌治疗提供新的治疗方法。本综述将探讨整合素在乳腺癌中的作用的现有知识。