title: The role of c-Src in integrin (α6β4) dependent translational control.
abstract: BACKGROUND
  Integrin α6β4 contributes to cancer progression by stimulating transcription as well as translation of cancer related genes. Our previous study demonstrated that α6β4 stimulates translation initiation of survival factors such as VEGF by activating mTOR pathway. However, the immediate early signaling events that link α6β4 to mTOR activation needs to be defined.
  
  
  RESULTS
  In the current studies, we demonstrated that c-Src is an immediate early signaling molecule that acts upstream of α6β4 dependent mTOR activation and subsequent translation of VEGF in MDA-MB-435/β4 and MDA-MB-231 cancer cells. m7GTP-Sepharose-binding assay revealed that Src activity is required to form eIF4F complex which is necessary for Cap-dependent translation in α6β4 expressing human cancer cells.
  
  
  CONCLUSIONS
  Overall, our studies suggest that integrin β4 and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF.
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Nadejda
authors.initials: N
authors.lastname: Korneeva
authors.forename: Tae Hyong
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Physiology and Stephenson Cancer Center, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA. Jun-Chung@ouhsc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Chung
mesh_terms: D001681:Biological Assay; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039161:Integrin alpha6beta4 / Q000235:genetics* / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational; D011485:Protein Binding; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D039161:Integrin alpha6beta4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D058570:TOR Serine-Threonine Kinases