PAK5 promotes the migration and invasion of cervical cancer cells by phosphorylating SATB1
PAK5 promotes the migration and invasion of cervical cancer cells by phosphorylating SATB1
复制标题
PAK5通过磷酸化SATB1促进宫颈癌细胞迁移和侵袭
DOI：
10.1038/s41418-018-0178-4
复制
发表时间：
2019-06-01
影响因子：
12.4
通讯作者：
Pei, Dong-Sheng
中科院分区：
文献类型：
--
作者：
Huo, Fu-Chun;Pan, Yao-Jie;Pei, Dong-Sheng
p21 激活激酶 5 (PAK5) 参与多种致癌信号传导通路，在多种类型的癌症中均发现其扩增或过度表达；然而，PAK5 在宫颈癌 (CC) 中的病理生理学作用仍然难以捉摸。本研究旨在阐明PAK5对CC转移的影响及其具体调控机制。我们进行了蛋白质印迹和免疫组织化学 (IHC) 分析，发现 PAK5 的表达水平在 CC 细胞和组织中显着上调。此外，通过 IHC 进行的统计分析表明，PAK5 的增加与 CC 进展显着相关。利用 Mn2+-Phos-tag SDS-PAGE、蛋白质印迹、免疫荧光和双荧光素酶报告基因测定来确定 SATB1 在 PAK5 介导的上皮间质转化 (EMT) 中的参与。我们发现PAK5介导的Ser47上特殊的富含AT的结合蛋白1（SATB1）磷酸化启动EMT级联并促进CC细胞的迁移和侵袭。此外，PAK5的过度表达在异种移植模式中诱导CC细胞的肺转移。综上所述，我们得出结论，PAK5 是一种新型预后指标，在 CC 转移中发挥重要作用。
p21-activated kinase 5 (PAK5) is involved in several oncogenic signaling pathways and its amplification or overexpression has been found in various types of cancer; however, the pathophysiologic role of PAK5 in cervical cancer (CC) remains elusive. This study aims to elucidate the effects of PAK5 on CC metastasis and its specific regulation mechanism. We performed western blotting and immunohistochemistry (IHC) analysis and found that the expression levels of PAK5 were significantly upregulated in CC cells and tissues. In addition, statistical analysis via IHC showed that increased PAK5 significantly correlated with CC progression. Mn2+-Phos-tag SDS-PAGE, western blotting, immunofluorescence and dual luciferase reporter assays were utilized to determine the involvement of SATB1 in PAK5-mediated epithelial–mesenchymal transition (EMT). We found that PAK5-mediated special AT-rich binding protein-1 (SATB1) phosphorylation on Ser47 initiated EMT cascade and promoted migration and invasion of CC cells. Furthermore, overexpression of PAK5 induced lung metastasis of CC cells in xenograft modes. Taken together, we conclude that PAK5 is a novel prognostic indicator and plays an important role in the CC metastasis.