Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, PR China.
Oncol Rep. 2012 May;27(5):1435-42. doi: 10.3892/or.2012.1664. Epub 2012 Jan 27.
P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. However, the role of Pak1 in gastric cancer metastasis remains unclear. Here, we showed that Pak1 is overexpressed in gastric cancer tissues from 74 patients by immunohistochemistry. Overexpression of Pak1 was associated with metastasis and prognosis of gastric cancer. In addition, overexpression of Pak1 increased gastric cancer cell motility and invasion, whereas downregulation of Pak1 expression reduced gastric cancer cell migration and invasion. In further study, data showed that activated Pak1 inhibited stress fiber and focal adhesion complex formation in gastric cancer cells and led to the formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of the ERK and JNK-dependent pathway in gastric cancer cell lines. In conclusion, our results suggest that Pak1 is overexpressed in gastric cancer and plays an important role in the metastasis of gastric cancer. The mechanism by which Pak1 induces cancer metastasis may involve activation of ERK and JNK.
P21 激活蛋白激酶（Pak1）是小 Rho GTPases 的主要下游效应物，在细胞形态发生、运动、有丝分裂和血管生成的调节中发挥重要作用。然而，Pak1 在胃癌转移中的作用尚不清楚。在这里，我们通过免疫组织化学显示 Pak1 在 74 例胃癌组织中过表达。Pak1 的过表达与胃癌的转移和预后有关。此外，Pak1 的过表达增加了胃癌细胞的迁移和侵袭能力，而 Pak1 表达的下调则降低了胃癌细胞的迁移和侵袭能力。进一步的研究数据表明，激活的 Pak1 抑制了胃癌细胞中应激纤维和黏着斑复合物的形成，并导致了运动表型的形成。重要的是，激活的 Pak1 引发了胃癌细胞系中 ERK 和 JNK 依赖性途径的磷酸化。总之，我们的研究结果表明，Pak1 在胃癌中过表达，并在胃癌的转移中发挥重要作用。Pak1 诱导癌症转移的机制可能涉及 ERK 和 JNK 的激活。
