Src kinase is commonly overexpressed in cancers and typically localized to the inner leaflet of the plasma membrane in normal cells. Now, Delaveris et al. have found that Src gets mislocalized to the extracellular surface and remodels the phosphoproteome on the surface of cancer cells.

Using photo-proximity labeling proteomics, the team probed for differentially expressed proteins on the surface of a human breast cancer cell line, identifying 738 proteins, of which 28 were kinases. They focused on Src, which was found to be expressed on the cell surface and to extracellularly phosphorylate cancer-associated substrates such as ADAM17 to alter cell proliferation.