Laboratory of Human Anatomy and Cell Biology, Faculty of Health Sciences, Tsukuba University of Technology, 305-8521 Tsukuba, Japan.
Discov Med. 2024 Oct;36(189):1998-2012. doi: 10.24976/Discov.Med.202436189.184.
This review predominantly acquaints the role of focal adhesion kinase (FAK) and cellular-Src (c-Src) in cell adhesion. Cell adhesion is a crucial phenomenon that causes the cells to interact with the extracellular matrix (ECM) or with each other. There are different proteins involved in cell adhesion including cell adhesion molecules (CAMs)/receptors that are present on the cell surface and various cytoplasmic proteins. FAK and c-Src are two proteins in the cytoplasm, which serve as regulators of different proteins involved in cell adhesion. They activate talin, vinculin and paxillin in turn connect the integrins with the cytoskeleton and in this way strengthen the integrin interaction with ECM. FAK-Src signalling also modulates cell-cell adhesion by regulating actin interactions. Being a key modulator of cell adhesion, FAK and c-Src signalling are linked with different pathological conditions like cancer, cardiovascular diseases, and embryonic developmental disorders. Thus, comprehensive research into FAK-Src signalling is of great importance in the exploration of different signalling targets for therapeutic interpretations. Different inhibitors and antibodies against various cell adhesion proteins, such as FAK, c-Src, and integrins, have already been used in preclinical and clinical trials to treat a variety of diseases, including cancer and chronic inflammatory conditions. Furthermore, this review presents different challenges to FAK-Src and cell adhesion signalling targeted drug development, which include, cytotoxicity and cell resistance to the drug. Finally, this review remarks that FAK and c-Src are important regulators of cell adhesion and are linked to various pathologies, nevertheless, more comprehensive research on these proteins would be a significant step forward in the development of effective therapies for the diseases associated with them.
这篇综述主要介绍了粘着斑激酶（FAK）和细胞质Src（c-Src）在细胞黏附中的作用。细胞黏附是一种导致细胞与细胞外基质（ECM）或彼此相互作用的关键现象。细胞黏附有不同的蛋白质参与，包括细胞黏附分子（CAMs）/受体，它们存在于细胞表面和各种细胞质蛋白质。FAK 和 c-Src 是细胞质中的两种蛋白质，作为参与细胞黏附的不同蛋白质的调节剂。它们依次激活粘着斑蛋白、纽蛋白和桩蛋白，将整合素与细胞骨架连接起来，从而增强整合素与 ECM 的相互作用。FAK-Src 信号还通过调节肌动蛋白相互作用来调节细胞-细胞黏附。作为细胞黏附的关键调节剂，FAK 和 c-Src 信号与不同的病理状况有关，如癌症、心血管疾病和胚胎发育障碍。因此，对 FAK-Src 信号的全面研究对于探索不同的信号靶点以进行治疗解释非常重要。已经在临床前和临床试验中使用了针对各种细胞黏附蛋白的不同抑制剂和抗体，如 FAK、c-Src 和整合素，以治疗各种疾病，包括癌症和慢性炎症性疾病。此外，本综述还提出了针对 FAK-Src 和细胞黏附信号靶向药物开发的不同挑战，包括细胞毒性和细胞对药物的耐药性。最后，本综述指出，FAK 和 c-Src 是细胞黏附的重要调节剂，与各种病理状况有关，但对这些蛋白质进行更全面的研究将是开发与这些蛋白质相关疾病的有效治疗方法的重要一步。
