WDR1 Promotes Cell Growth and Migration and Contributes to Malignant Phenotypes of Non-small Cell Lung Cancer through ADF/cofilin-mediated Actin Dynamics.
WDR1 Promotes Cell Growth and Migration and Contributes to Malignant Phenotypes of Non-small Cell Lung Cancer through ADF/cofilin-mediated Actin Dynamics.
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WDR1 通过 ADF/cofilin 介导的肌动蛋白动力学促进细胞生长和迁移并导致非小细胞肺癌的恶性表型
DOI：
10.7150/ijbs.23845
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发表时间：
2018
影响因子：
9.2
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Yuan B;Zhang R;Hu J;Liu Z;Yang C;Zhang T;Zhang C
肿瘤的特点是细胞的迁移和侵袭，这涉及到很强的肌动蛋白动力学。肌动蛋白动力学的调节与癌细胞迁移和肿瘤进展有关。WDR1(WD-Repeat结构域1)是肌动蛋白解聚因子(ADF)/cofilin的主要辅因子，强烈促进ADF/cofilin介导的肌动蛋白分解。WDR1在非小细胞肺癌(NSCLC)进展中的作用尚不清楚。在这里，我们发现WDR1在人非小细胞肺癌组织中的表达水平高于癌旁组织，并且高水平的WDR1与NSCLC患者的预后不良相关。在体内外，非小细胞肺癌细胞中WDR1基因的敲除显著抑制细胞的迁移、侵袭、EMT过程和肿瘤细胞的生长。另外，WDR1的过表达促进了NSCLC细胞的增殖和迁移。在机制上，我们的数据提示WDR1可能通过肌动蛋白细胞骨架介导的YAP调控肿瘤细胞的增殖和迁移，并且我们证明了WDR1通过ADF/cofilin介导的肌动蛋白分解参与了NSCLC的进展。我们的发现暗示ADF/cofilin-WDR1-actin轴是恶性表型的激活因子，有望成为肺癌的治疗靶点。
The characteristic of carcinoma is cell migration and invasion, which involve in strong actin dynamics. Regulations of actin dynamics have been implicated in cancer cell migration and tumor progression. WDR1 (WD-repeat domain 1) is a major cofactor of the actin depolymerizing factor (ADF)/cofilin, strongly accelerating ADF/cofilin-mediated actin disassembly. The role of WDR1 in non-small cell lung cancer (NSCLC) progression has been unknown. Here, we show that the expression levels of WDR1 are increased in human NSCLC tissues compared with adjacent non-tumor tissues, and high WDR1 level correlates with poor prognosis in NSCLC patients. Knockdown of WDR1 in NSCLC cells significantly inhibits cell migration, invasion, EMT process and tumor cell growth in vitro and in vivo. Otherwise, overexpression of WDR1 promotes NSCLC cell proliferation and migration. Mechanically, our data suggested WDR1 regulated tumor cells proliferation and migration might through actin cytoskeleton-mediated regulation of YAP, and we demonstrated that WDR1 contributes to NSCLC progression through ADF/cofilin-mediated actin disassembly. Our findings implicate that the ADF/cofilin-WDR1-actin axis as an activator of malignant phenotype that will be a promising therapeutic target in lung cancer.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
8.8
作者：
Qiao, Yiting;Chen, Jianxiang;Sudol, Marius
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影响因子：
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作者：
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