P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis

Oncol Rep. 2012 May;27(5):1435-42. doi: 10.3892/or.2012.1664. Epub 2012 Jan 27.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Enzyme Activation
  • Female
  • Gene Expression
  • Gene Silencing
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • RNA, Small Interfering / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stress Fibers / genetics
  • p21-Activated Kinases / genetics*
  • p21-Activated Kinases / metabolism

Substances

  • RNA, Small Interfering
  • p21-Activated Kinases