Proteomic Profiling of Signaling Proteins in Ten Different Tumor Cell Lines

Normal cell development requires a coordinated and organised reaction and adaptation to the constantly changing environment. Cells achieve this by a network of signaling pathways comprising proteins that serve as molecular switches. Subversion of these intracellular signaling pathways is implicated in several diseases, including cancer. To better understand the mechanisms of this process and to identify potential biomarkers and/or therapeutic targets at the protein level, we performed two-dimensional electrophoresis (2-DE) and mass spectrometry in ten different tumor cell lines. Following separation by high resolution 2-DE, a series of seventy signaling proteins were unambiguously identified that were differentially expressed in different cell lines. Signaling proteins of immense significance in cancer biology including two proteins of the 14-3-3 protein family, growth factor receptor bound protein 2, Cdc25B phosphatase, disheveled associated activator of morphogenesis-1, putative ORF1, zyxin, phosphatidylethanolamine-binding protein, Rho/Rab GDP-dissociation inhibitors, Stam binding protein, SH3 domain GRB2-like protein B2, Cullin homolog 3, Coronin-1B, calcium binding proteins and enzymes with signaling function displayed tumor cell line-specific expression. Other signaling proteins of importance, such as maspin, nucleoside diphosphate kinase-A, Ser/Thr kinases, Ser/Thr phosphatases, septins, annexins and receptor for hyaluronic acid-mediated motility, however, showed tumor cell line-associated expression. These data highlight that there might be specific and shared signaling pathways that are activated in the chain of events leading to tumor formation. Moreover, the data open up the possibility of developing new prognostic markers, as well as widening the avenue of cancer chemotherapy.