Lane Jane, Martin Tracey, Weeks Hoi Ping, Jiang Wen Guo
Cardiff University-Peking University Cancer Institute, Henry Wellcome Building, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
Cancer Genomics Proteomics. 2014 May-Jun;11(3):155-65.
A major factor controlling the metastatic nature of cancer cells is their motility. Alterations in the signalling pathways controlling its regulation can lead to tumor cell invasion and metastasis. Directional motility involves protrusion of the cell's leading edge, via formation of filopodia and lamellipodia, adhesion to the substrate followed by tail retraction and de-adhesion. Rho GTPase binding proteins function as activators of the actin cytoskeleton and are key players in the transendothelial migration of cancer cells. Activation of the specific GTPases Rho, Rac1 and Cdc42 results in formation of actin stress fibres, membrane ruffles, lamellipodia and filopodia respectively and in cortical actin assembly. Pathways through which Rho GTPases elicit these effects are through direct interaction with members of the Wiskott-Alrich Syndrome Protein (WASP) family which stimulates structures such as lamellipodia and filopodia. The present review explores the role and function of Rho GTPases, WASP and WAVE in cancer metastasis.
控制癌细胞转移特性的一个主要因素是其运动性。控制其调节的信号通路发生改变会导致肿瘤细胞侵袭和转移。定向运动涉及细胞前缘的突出，通过丝状伪足和片状伪足的形成，与底物粘附，随后尾部收缩和去粘附。Rho GTPase结合蛋白作为肌动蛋白细胞骨架的激活剂，是癌细胞跨内皮迁移的关键参与者。特定的GTPases Rho、Rac1和Cdc42的激活分别导致肌动蛋白应力纤维、膜皱褶、片状伪足和丝状伪足的形成以及皮质肌动蛋白组装。Rho GTPases引发这些效应的途径是通过与威斯科特-奥尔德里奇综合征蛋白（WASP）家族成员直接相互作用，该家族刺激片状伪足和丝状伪足等结构。本综述探讨了Rho GTPases、WASP和WAVE在癌症转移中的作用和功能。
