Comprehensive analysis of proteomic landscape remodeling during carcinogenesis

We have performed a comprehensive analysis of how oncogenic transformation induced by v-Src kinase remodels the proteomic landscape of human breast epithelial (MCF10A) cells. We characterised the proteome of untransformed cells to a depth of ~14,000 proteins, spanning a wide dynamic range of expression levels. Changes in both protein abundance and protein turnover were analysed, in biological triplicate, at seven time points spanning 1-72 hours post v-Src activation, coincident with profound phenotypic changes in cell behaviour and morphology. These data are provided for interactive exploration via the Encyclopedia of Proteome Dynamics database (www.peptracker.com/epd). We detect only a small subset (<3%) of mostly low copy number proteins showing altered abundance and/or half-life after transformation, including proteins regulated at the post-transcriptional level. Src activation modulated proteins with diverse cellular functions and with differential response kinetics. The resulting ‘Src signature’ is shown to be prognostic of reduced cancer patient survival post diagnosis.