Rho kinase proteins--pleiotropic modulators of cell survival and apoptosis.
Rho kinase proteins--pleiotropic modulators of cell survival and apoptosis.
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发表时间：
2011-11
影响因子：
2
通讯作者：
Catharine A Street;B. Bryan
中科院分区：
文献类型：
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作者：
Catharine A Street;B. Bryan
Rho激酶（ROCK）蛋白是Rho- gtpase激活的丝氨酸/苏氨酸激酶，通过调节Lin11、is -1和Mec-3结构域（LIM）激酶、肌球蛋白轻链（MLC）和MLC磷酸酶，作为肌动蛋白-肌球蛋白细胞骨架动力学的调节剂。文献中已经报道了细胞骨架重排与肿瘤细胞侵袭、转移和微环境相互作用解除之间的强相关性，许多制药公司正在积极寻求利用ROCK信号的药理抑制剂治疗癌症。事实上，在许多临床前模型中，ROCK抑制剂已经显示出显著的抑制肿瘤生长和转移的功效。有趣的是，ROCK信号已被证明以细胞类型和环境依赖的方式促进凋亡或促进存活，尽管控制ROCK介导的细胞命运决定的分子机制尚不清楚。这篇综述总结了ROCK信号在生存和凋亡中的多种作用，并表明肿瘤细胞中ROCK活性的控制调节有可能显著影响肿瘤生存和患者预后。
Rho kinase (ROCK) proteins are Rho-GTPase activated serine/threonine kinases that function as modulators of actin-myosin cytoskeletal dynamics via regulation of Lin11, Isl-1 & Mec-3 domain (LIM) kinase, myosin light chain (MLC), and MLC phosphatase. A strong correlation between cytoskeletal rearrangements and tumor cell invasion, metastasis, and deregulated microenvironment interaction has been reported in the literature, and the utilization of pharmacological inhibitors of ROCK signaling for the treatment of cancer is actively being pursued by a number of pharmaceutical companies. Indeed, in many preclinical models ROCK inhibitors have shown remarkable efficacy in reducing tumor growth and metastasis. Interestingly, ROCK signaling has been shown to be either pro-apoptotic or pro-survival in a cell type and context dependent manner, though the molecular mechanisms controlling ROCK-mediated cell fate decisions are unknown. This review summarizes the many pleiotropic roles of ROCK signaling in survival and apoptosis, and suggests that controlled modulation of ROCK activity in tumor cells has the potential to significantly affect tumor survival and patient outcome.