p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5
p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5
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p21 激活激酶 6 通过调节 Eg5 控制有丝分裂和肝细胞癌进展
DOI：
10.1016/j.bbamcr.2020.118888
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发表时间：
2021-02-01
影响因子：
5.1
通讯作者：
Du，Xiaojuan
中科院分区：
文献类型：
--
作者：
Zheng，Jiaojiao;Zhang，Chunfeng;Du，Xiaojuan
P21激活激酶6（PAK 6）与癌症中的许多基本细胞过程相关，包括细胞-细胞粘附、迁移和凋亡。在这里，我们报告了PAK 6在有丝分裂中的一个新功能。PAK 6峰在M期的表达。PAK 6的敲低增加G2/M期的细胞数量并促进细胞增殖。PAK 6与Eg 5特异性共定位于中心体。PAK 6的耗尽导致多极纺锤体和Eg 5的同时上调。此外，PAK 6耗竭诱导的多纺锤体和细胞周期进程通过Eg 5的敲低而逆转。这些数据表明PAK 6通过调节Eg 5表达来调节纺锤体形成和细胞周期。此外，当Eg 5被下调或抑制时，PAK 6的表达上调。因此，PAK 6和Eg 5相互负调节。值得注意的是，PAK 6表达对HCC患者结局的影响受Eg 5表达控制。Eg 5的抑制逆转PAK 6消耗促进的细胞侵袭。总的来说，我们的数据表明PAK 6和Eg 5之间的相互调节可能促进HCC的进展。
P21-activated kinases 6 (PAK6) associated with many fundamental cellular processes in cancer including cell-cell adhesion, migration and apoptosis. Here, we report a novel function of PAK6 in mitosis. Expression of PAK6 peaks in the M phase. Knockdown of PAK6 increases cell number in G2/M and promotes cell proliferation. PAK6 specifically colocalizes with Eg5 in the centrosome. Depletion of PAK6 results in multipolar spindle and a simultaneous upregulation of Eg5. Further, the PAK6 depletion-induced multiple spindle and cell cycle progression is reversed by knockdown of Eg5. These data suggest that PAK6 regulates spindle formation and cell cycle by regulating Eg5 expression. Additionally, expression of PAK6 is upregulated when Eg5 is downregulated or inhibited. Thus, PAK6 and Eg5 negatively inter-regulate each other. Significantly, the effect of PAK6 expression on the outcome of the HCC patients is controlled by Eg5 expression. Inhibition of Eg5 reverses PAK6 depletion-promoted cell invasion. Collectively, our data indicate that the inter-regulation between PAK6 and Eg5 might promote the progression of HCC.