Ottawa Hospital Research Institute, Cancer Therapeutics, Ottawa, ON Canada.
Cell Adh Migr. 2013 Jan-Feb;7(1):1-10. doi: 10.4161/cam.22495. Epub 2012 Nov 15.
Reorganization of the cytoskeleton is necessary for apoptosis, proliferation, migration, development and tissue repair. However, it is well established that mutations or overexpression of key regulators contribute to the phenotype and progression of several pathologies such as cancer. For instance, c-src mutations and the overexpression of FAK have been implicated in the invasive and metastatic process, suggesting that components of the motility system may represent a new class of therapeutic targets. Over the last several years, we and others have established distinct roles for the Ste20-like kinase SLK, encompassing apoptosis, growth, motility and development. Here, we review the SLK field from its initial cloning to the most recent findings from our laboratory. We summarize the various roles of SLK and the biochemical mechanisms that regulate its activity. These various findings reveal very complex functions and pattern of regulation for SLK in development and cancer, making it a potential therapeutic target.
细胞骨架的重排对于细胞凋亡、增殖、迁移、发育和组织修复是必需的。然而,已有充分的证据表明,关键调控因子的突变或过表达会导致多种病理状况(如癌症)的表型和进展。例如,c-src 突变和粘着斑激酶(FAK)的过表达已被牵涉到浸润和转移过程中,这表明运动系统的成分可能代表一类新的治疗靶点。在过去的几年中,我们和其他人已经确立了丝裂原活化蛋白激酶激酶样激酶(SLK)在细胞凋亡、生长、运动和发育中的独特作用。在这里,我们从最初的克隆到我们实验室的最新发现,回顾了 SLK 领域。我们总结了 SLK 的各种作用以及调节其活性的生化机制。这些不同的发现揭示了 SLK 在发育和癌症中非常复杂的功能和调控模式,使其成为一个有潜力的治疗靶点。