title: RACK1 inhibits the serum- and anchorage-independent growth of v-Src transformed cells.
abstract: 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.
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Mamidipudi
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Chang
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Harte
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Lee
authors.forename: Christine A
authors.initials: CA
authors.lastname: Cartwright
mesh_terms: 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
chemical_list: 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