Quantitative phosphoproteomics reveals a cluster of tyrosine kinases that mediates SRC invasive activity in advanced colon carcinoma cells.

摘要: The nonreceptor tyrosine kinase Src is frequently overexpressed and/or activated in human colorectal carcinoma (CRC), and its increased activity has been associated with a poor clinical outcome. implicated growth invasion of these cancer cells by still not well-known mechanisms. Here, we addressed oncogenic signaling using quantitative phosphoproteomics. overexpression invasiveness metastatic SW620 CRC cells. Stable isotope labeling amino acids cell culture combination liquid chromatography tandem mass spectrometry allowed the identification 136 proteins which exhibited significant increase association phosphorylation upon expression. These mainly include signaling, cytoskeleton, vesicular-associated proteins. Interestingly, also phosphorylated cluster kinases, i.e., receptors Met EphA2, cytoplasmic Fak, pseudo-tyrosine SgK223, were required for invasive activity. Similar results obtained Colo205 that exhibit high endogenous We concluded uses kinases network to promote this implicates reverse via receptors. Targeting may be therapeutic value cancer.