title: 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.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Po-Chao
authors.initials: PC
authors.lastname: Chan
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D006224:Cricetinae; D004285:Dogs; D004789:Enzyme Activation; D006056:Golgi Apparatus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D020729:p120 GTPase Activating Protein / Q000235:genetics / Q000378:metabolism*; D048490:raf Kinases / Q000378:metabolism; D020725:ral GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D020729:p120 GTPase Activating Protein; D048490:raf Kinases; D020725:ral GTP-Binding Proteins; D018631:ras Proteins; D019061:src-Family Kinases; C000631346:CSK protein, human