JWA as a functional molecule to regulate via MAPK cascades and F-actin cancer cells migration cytoskeleton
JWA as a functional molecule to regulate via MAPK cascades and F-actin cancer cells migration cytoskeleton
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DOI：
10.1016/j.cellsig.2007.01.007
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Zhou, Jianwei
中科院分区：
文献类型：
--
作者：
Chen, Hairong;Bai, Jin;Zhou, Jianwei
丝裂原活化蛋白激酶（MAPK）级联被认为介导多种生物学功能，如细胞生长，分化和迁移。活化的MAPK可影响微管（MT），其对细胞极性、分化和运动是必需的。本研究的数据表明，JWA，一个新发现的微管相关蛋白（MAP）是必不可少的F-actin细胞骨架的重排和MAPK级联的激活三氧化二砷（As 2 O3）和佛波酯（PMA）诱导。JWA单独在HeLa、B16和HCCLM 3癌细胞中的过表达有效地抑制细胞迁移;而当细胞缺乏JWA表达时，细胞迁移显著加速。这些现象的机制可能是由于JWA影响F-肌动蛋白重排。此外，JWA缺陷阻断了As_2O_3产生的抗迁移作用，但增强了PMA启动的HeLa细胞迁移作用。JWA SDR-SLR基序不仅对MAPK级联激活至关重要，而且对细胞迁移也至关重要。进一步的研究发现，JWA通过ERK下游效应物粘着斑激酶（FAK）和环氧合酶-2（考克斯-2）差异调节细胞迁移。因此，JWA调节肿瘤细胞迁移可能涉及MAPK级联激活和F-actin细胞骨架重排机制。我们的数据提供了一个意想不到的作用，JWA在肿瘤细胞迁移行为。(c)2007爱思唯尔公司All rights reserved.
Mitogen activated protein kinase (MAPK) cascades are thought to mediate diverse biological functions such as cell growth, differentiation and migration. Activated MAPK may affect microtubule (MT) which is essential for cellular polarity, differentiation and motility. Data in this study show that JWA, a newly identified novel microtubule-associated protein (MAP) was essential for the rearrangement of F-actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As2O3) and phorbol ester (PMA). Over-expression of JWA alone in HeLa, B16 and HCCLM3 cancer cells effectively inhibited cellular migration; whereas, cellular migration was significantly accelerated when cells were deficient in JWA expression. The mechanism underlying these phenomena might be due to JWA affected F-actin rearrangement. Furthermore, JWA deficiency blocked anti-migratory effect produced by As2O3 but enhanced the migratory effect initiated by PMA in HeLa cells. JWA SDR-SLR motifs are not only critical for the MAPK cascades activation, but also for cell migration. Further studies found that JWA differentially regulated cell migration via ERK downstream effectors focal adhesion kinase (FAK) and cyclooxygenase-2 (COX-2). Therefore, JWA regulated-tumor cellular migration might involve MAPK cascades activation and F-actin cytoskeleton rearrangement mechanisms. Our data provide an unexpected role for JWA in tumor cell migration behaviors. (c) 2007 Elsevier Inc. All rights reserved.