title: Cell density modulates SHC3 expression and survival of human glioblastoma cells through Fak activation.
abstract: Shc3 protein levels are high in human glioblastoma but they decrease in vitro. We found that SHC3 mRNA and protein increased when glioblastoma cells grew as multicellular tumor spheroid (MTS). Shc3 expression was also induced in adherent cultures by increasing cell density. Among the Shc family members, only Shc2 and Shc3 increased with cell density. Shc3 and focal adhesion kinase (Fak) interact as shown by co-immunoprecipitation. Inhibition of Fak activation reduced Shc3 increase and MTS formation and changed Shc3 phosphorylation pattern. Our results suggest that in gliomas cell density modulates Shc3 protein levels and its activity, at least in part, through Fak activation.
authors: Neurosurgery, Dipartimento di Scienze Clinico-Chirurgiche e Pediatriche, Università degli Studi di Pavia, Fondazione IRCCS Policlinico S. Matteo, 27100, Pavia, Italy.
authors: Alberto
authors: A
authors: Azzalin
authors: Elena
authors: E
authors: Moretti
authors: Eloisa
authors: E
authors: Arbustini
authors: Lorenzo
authors: L
authors: Magrassi
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002452:Cell Count; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C099021:SHC2 protein, human; C122029:SHC3 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D051416:Focal Adhesion Protein-Tyrosine Kinases