p120RasGAP-mediated activation of c-Src is critical for oncogenic Ras to induce tumor invasion.

Abstract

Ras genes are the most common targets for somatic gain-of-function mutations in human cancers. In this study, we found a high incidence of correlation between Ras oncogenic mutations and c-Src activation in human cancer cells. We showed that oncogenic Ras induces c-Src activation mainly on the Golgi complex and endoplasmic reticulum. Moreover, we identified p120RasGAP as an effector for oncogenic Ras to activate c-Src. The recruitment of p120RasGAP to the Golgi complex by oncogenic Ras facilitated its interaction with c-Src, thereby leading to c-Src activation, and this p120RasGAP-mediated activation of c-Src was important for tumor invasion induced by oncogenic Ras. Collectively, our findings unveil a relationship between oncogenic Ras, p120RasGAP, and c-Src, suggesting a critical role for c-Src in cancers evoked by oncogenic mutations in Ras genes.

• Authors: Po-Chao Chan, Hong-Chen Chen
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 9 Pg. 2405-15 (May 01 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22411953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR

Chemical References

• Reactive Oxygen Species
• p120 GTPase Activating Protein
• Protein-Tyrosine Kinases
• CSK Tyrosine-Protein Kinase
• src-Family Kinases
• CSK protein, human
• raf Kinases
• ral GTP-Binding Proteins
• ras Proteins

Topics

• Animals
• CSK Tyrosine-Protein Kinase
• Cell Adhesion (physiology)
• Cell Line, Tumor
• Cricetinae
• Dogs
• Enzyme Activation
• Golgi Apparatus (enzymology, genetics, metabolism)
• HEK293 Cells
• Humans
• Mice
• NIH 3T3 Cells
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Reactive Oxygen Species (metabolism)
• Transfection
• p120 GTPase Activating Protein (genetics, metabolism)
• raf Kinases (metabolism)
• ral GTP-Binding Proteins (metabolism)
• ras Proteins (genetics, metabolism)
• src-Family Kinases