Naser Rayan, Aldehaiman Abdullah, Díaz-Galicia Escarlet, Arold Stefan T
King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Division of Biological and Environmental Sciences and Engineering (BESE), Thuwal 23955-6900, Saudi Arabia.
Cancers (Basel). 2018 Jun 11;10(6):196. doi: 10.3390/cancers10060196.
Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled via modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved in this control are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and with particular focus on how these mechanisms could inspire or improve anticancer therapies.
粘着斑激酶（FAK）及其紧密同源物富含脯氨酸的酪氨酸激酶2（PYK2）是癌细胞侵袭性扩散和转移的关键调节因子。虽然已发现FAK和PYK2的靶向小分子抑制剂具有有前景的抗肿瘤活性，但癌细胞逃避抗激酶药物的强大能力可能会削弱它们的临床长期疗效。在健康细胞中，FAK和PYK2的表达和/或功能通过基因表达的调节、竞争性可变剪接形式、非编码RNA以及直接或间接影响激酶激活或蛋白质稳定性的蛋白质来严格控制。参与这种调控的分子因子在癌细胞中经常失调。在这里，我们综述了控制FAK和PYK2的内源性机制，特别关注这些机制如何启发或改善抗癌治疗。
