Fig. 1.

Expansion of the SDF-1/CXCR4 migratory signaling network in breast cancer stem cells. Using a model of human breast cancer, Yi el al. (2) isolated cells with tumor-initiating capacity (i.e., cancer stem cells). Following stimulation with SDF-1, the authors used quantitative (isotope reductive dimethylation) LC-MS to identify and quantify over 11,000 protein phosphorylation sites. This analysis revealed many previously unrecognized downstream phosphorylation events involving 60 cell mobility-related proteins, 50 kinases, and 8 negative-feedback regulators, of which 43, 44, and 6 proteins, respectively, had not been previously associated with SDF-1/CXCR4 signaling. To derive biological insight from this complex data, the authors used computational methods to integrate their phospho-proteomic data with known pathways from the literature, which allowed for identification of a novel PKA-MAPK2K-ERK pathway. Purple circles represent measured phosphorylation sites.