P21-activated protein kinase 1 induces colorectal cancer metastasis involving ERK activation and phosphorylation of FAK at Ser-910
P21-activated protein kinase 1 induces colorectal cancer metastasis involving ERK activation and phosphorylation of FAK at Ser-910
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DOI：
10.3892/ijo_00000746
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发表时间：
2010-10-01
影响因子：
5.2
通讯作者：
Liu, Bing-Ya
中科院分区：
文献类型：
--
作者：
Li, Liang-Hui;Zheng, Min-Hua;Liu, Bing-Ya
Pak 1在结直肠癌中过表达，但其在结直肠癌中的作用尚不清楚。在这项研究中，Pak 1的表达和活性与大肠癌的侵袭行为有关。Pak 1的过表达增加了结直肠癌细胞的运动性和侵袭性，而Pak 1表达或活性的下调减少了结直肠癌细胞的迁移和侵袭。此外，激活的Pak 1抑制结直肠癌细胞中应力纤维和粘着斑复合物的形成，并导致形成运动表型。重要的是，在结直肠癌细胞系和临床样品中，活化的Pak 1通过ERK依赖性途径引起FAK在Ser-910的磷酸化。总之，我们的研究结果表明，激活Pak 1调节大肠癌转移需要ERK依赖的磷酸化FAK在Ser-910。
Pak1 has been reported to be overexpressed in colorectal cancer, but the role of Pak1 in colorectal cancer remains unclear. In this study, Pak1 expression and activity were associated with aggressive behavior of colorectal cancer. Overexpression of Pak1 increased colorectal cancer cell motility and invasion, whereas down-regulation of Pak1 expression or activity reduced colorectal cancer cell migration and invasion. In addition, activated Pak1 inhibited stress fiber and focal adhesion complex formation in colorectal cancer cells and led to formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of FAK at Ser-910 via an ERK-dependent pathway in colorectal cancer cell lines and clinical samples. In conclusion, our results suggest that activated Pak1 regulates colorectal cancer metastasis requiring an ERK-dependent phosphorylation of FAK at Ser-910.