RACK1 inhibits the serum- and anchorage-independent growth of v-Src transformed cells.
Cancer cells are capable of serum- and anchorage-independent growth, and focus formation on monolayers of normal cells. Previously, we showed that RACK1 inhibits c-Src kinase activity and NIH3T3 cell growth. Here, we show that RACK1 partially inhibits v-Src kinase activity, and the serum- and anchorage-independent growth of v-Src transformed cells, but has no effect on focus formation. RACK1-overexpressing v-Src cells show disassembly of podosomes, which are actin-rich structures that are distinctive to fully transformed cells. Together, our results demonstrate that RACK1 overexpression in v-Src cells partially reverses the transformed phenotype of the cells. Our results identify an endogenous inhibitor of the oncogenic Src tyrosine kinase and of cell transformation.
Mamidipudi
Vidya
V
Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Chang
Betty Y
BY
Harte
Rachel A
RA
Lee
Kelly C
KC
Cartwright
Christine A
CA
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D003470:Culture Media; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D041681:NIH 3T3 Cells; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D044967:Serum; D014162:Transfection; D014170:Transformation, Genetic; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D003470:Culture Media; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010455:Peptides; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D000075370:Receptors for Activated C Kinase; C070301:peptide I; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); C496051:Ptk2 protein, mouse; D011493:Protein Kinase C