Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Int J Oncol. 2010 Oct;37(4):951-62.
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.
Pak1 已被报道在结直肠癌中过表达，但 Pak1 在结直肠癌中的作用仍不清楚。在这项研究中，Pak1 的表达和活性与结直肠癌的侵袭性行为有关。Pak1 的过表达增加了结直肠癌细胞的迁移和侵袭能力，而 Pak1 表达或活性的下调则降低了结直肠癌细胞的迁移和侵袭能力。此外，激活的 Pak1 抑制了结直肠癌细胞中应力纤维和焦点黏附复合物的形成，并导致了运动表型的形成。重要的是，激活的 Pak1 通过 ERK 依赖性途径在结直肠癌细胞系和临床样本中诱导 FAK 在 Ser-910 上的磷酸化。总之，我们的结果表明，激活的 Pak1 通过 ERK 依赖性途径在 Ser-910 上磷酸化 FAK 来调节结直肠癌转移。
