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LIM激酶(LIM kinase,LIMK)家族主要有两个成员:LIMK1和LIMK2,它们在癌症的侵袭和迁移过程中起着重要的作用。其通过调节cofilin家族蛋白的活性而影响肌动蛋白细胞骨架结构,对细胞形态、运动、黏附以及迁移都至关重要。LIMK对cofilin蛋白磷酸化与去磷酸化间的平衡进行微调节可能是影响肿瘤细胞迁移侵袭能力的决定性因素。LIMK受多条上游信号通路调控,主要上游信号分子是RhoGTP酶和Slingshot磷酸酶,形成Rho-ROCK/PAK-LIMK-Cofilin和SSH-LIMK-Cofilin信号通路。LIMK分布广泛并对多种组织的正常发育必不可少,在多种肿瘤组织中高表达并参与肿瘤生长、血管形成以及迁移侵袭过程。本文综述了LIMK的结构、功能、组织表达,参与肿瘤细胞迁移侵袭的机制以及信号通路的调控。
There are two major members of the LIM kinase (LIMK) family: LIMK1 and LIMK2, which play important roles in cancer invasion and migration. It affects the actin cytoskeleton architecture by modulating cofilin family activity and is crucial for cell morphology, motility, adhesion and migration. LIMK micro-regulation of the balance between cofilin phosphorylation and dephosphorylation may be the decisive factor affecting tumor cell migration and invasion. LIMK is regulated by multiple upstream signaling pathways. The major upstream signaling molecules are RhoGTPase and Slingshot phosphatase, forming the Rho-ROCK / PAK-LIMK-Cofilin and SSH-LIMK-Cofilin signaling pathways. LIMK is widely distributed and indispensable to the normal development of many tissues and is highly expressed in many tumor tissues and participates in tumor growth, angiogenesis and migration and invasion. This review summarizes the structure, function, tissue expression of LIMK, the mechanisms involved in tumor cell migration and invasion, and the regulation of signal pathways.