Contribution of phosphoproteomics in understanding SRC signaling in normal and tumor cells.

The membrane-anchored, non-receptor tyrosine kinase (non-RTK) SRC is a critical regulator of signal transduction induced by a large variety of cell-surface receptors, including RTKs that bind to growth factors to control cell growth and migration. When deregulated, SRC shows strong oncogenic activity, probably because of its capacity to promote RTK-mediated downstream signaling even in the absence of extracellular stimuli. Accordingly, SRC is frequently deregulated in human cancer and is thought to play important roles during tumorigenesis. However, our knowledge on the molecular mechanism by which SRC controls signaling is incomplete due to the limited number of key substrates identified so far. Here, we review how phosphoproteomic methods have changed our understanding of the mechanisms underlying SRC signaling in normal and tumor cells and discuss how these novel findings can be used to improve therapeutic strategies aimed at targeting SRC signaling in human cancer.