PC3细胞中WAVE1和-3与ARP2/3复合体之间的关联
The Association Between WAVE1 and -3 and the ARP2/3 Complex in PC 3 Cells.
作者信息
Weeks Hoi Ping, Sanders Andrew J, Kynaston Howard G, Jiang Wen G
机构信息
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
出版信息
Anticancer Res. 2016 Mar;36(3):1135-42.
BACKGROUND
Actin polymerisation is stimulated by the actin-related protein (ARP) 2/3 complex and drives cell migration. This complex is activated by Wiskott-Aldrich syndrome protein family (WASP) verprolin homologous protein (WAVE) proteins. WAVE1 and -3 have been implicated in the aggressiveness of metastatic prostate cancer cells.
MATERIALS AND METHODS
Cell growth, motility and invasion were analyzed in WAVE1- and WAVE3-knockdown PC-3 cells along with the ARP2/3 inhibitor, CK-0944636. Confocal microscopy was adopted to examine protein co-localisation. Immunoprecipitation approaches were used to determine protein tyrosine phosphorylation.
RESULTS
Cell growth suppression was observed with WAVE3 knockdown and ARP2/3 inhibition. Reduced cell invasion effects observed with WAVE1 knockdown appeared to be rescued by ARP2/3 inhibition. WAVE1 and WAVE3 and ARP2 co-localisation was lost in PC-3 WAVE-knockdown cells, while increased ARP2 tyrosine phosphorylation was observed with WAVE3 knockdown.
CONCLUSION
These results implicate a contributory role of WAVE1 and -3 to the metastatic phenotype of PC-3 cells through their interaction with the ARP2/3 complex.
背景
肌动蛋白聚合受肌动蛋白相关蛋白（ARP）2/3复合物刺激并驱动细胞迁移。该复合物由威斯科特-奥尔德里奇综合征蛋白家族（WASP）维普洛林同源蛋白（WAVE）激活。WAVE1和WAVE3与转移性前列腺癌细胞的侵袭性有关。
材料与方法
对WAVE1和WAVE3敲低的PC-3细胞以及ARP2/3抑制剂CK-0944636进行细胞生长、运动性和侵袭分析。采用共聚焦显微镜检查蛋白共定位。利用免疫沉淀方法测定蛋白酪氨酸磷酸化。
结果
观察到WAVE3敲低和ARP2/3抑制时细胞生长受到抑制。ARP2/3抑制似乎挽救了WAVE1敲低时观察到的细胞侵袭作用降低的现象。在PC-3 WAVE敲低细胞中，WAVE1和WAVE3与ARP2的共定位消失，而WAVE3敲低时观察到ARP2酪氨酸磷酸化增加。
结论
这些结果表明WAVE1和WAVE3通过与ARP2/3复合物相互作用对PC-3细胞的转移表型起作用。
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