title: [Analysis of oncogenic signaling induced by tyrosine kinases in tumors by SILAC-based quantitative proteomic approach].
abstract: Protein tyrosine kinases (TK) transmit intracellular signaling induced by many extracellular stimuli resulting in cell growth or adhesion. Deregulation of their activity leads to malignant cell transformation that plays an important role in human cancer. The signaling pathways involved in this oncogenic process are however only partially elucidated. Interestingly, SILAC-based quantitative proteomics allow the identification of the whole spectrum of TK substrates and the dynamic of phosphorylation state involved in oncogenic signaling. For example, this approach has highlighted the unsuspected complexity of the oncogenic signaling induced by the TK Src in colorectal cancer (CRC) cells. In this review, we describe a new SILAC-based technology applied to in vivo models of human tumors engrafted in nude mice. This method revealed significant differences between Src-oncogenic signaling of CRC cells in tumors and in culture. Finally, we discuss the interest of SILAC with recently described in vivo proteomic methods and in cancer, including the analysis of oncogenic signaling in tumor progression and the anti-tumoral activity of TK inhibitors in vivo.
authors.affiliation: CNRS UMR5237, université de Montpellier 1 et 2, centre de recherche de biochimie macromoléculaire (CRBM), 34000 Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sirvent
authors.affiliation: CNRS UMR5203, Inserm U661, université de Montpellier 1 et 2, institut de génomique fonctionnelle (IGF), plate-forme de protéomique fonctionnelle, 34000 Montpellier, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Urbach
authors.affiliation: CNRS UMR5237, université de Montpellier 1 et 2, centre de recherche de biochimie macromoléculaire (CRBM), 34000 Montpellier, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Roche
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D018929:Cell Culture Techniques; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000596:Amino Acids; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases