GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways

Int J Mol Sci. 2016 Apr 11;17(4):470. doi: 10.3390/ijms17040470.

Abstract

Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.

Keywords: GL-1196; PAK4; gastric cancer; small molecular compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Invasiveness
  • Signal Transduction / drug effects
  • Small Molecule Libraries / pharmacology*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • p21-Activated Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries
  • PAK4 protein, human
  • p21-Activated Kinases