Figure 1.

Novel role for autophagy downstream of oncogenic SRC in promoting focal adhesion disassembly and tumor cell motility. Analyses from primary human cancers and data from genetically engineered mouse models link autophagy to tumor progression to metastasis. However, the molecular mechanisms by which autophagy promotes metastasis are relatively unknown. Our work contributes to a greater understanding of how autophagy promotes metastasis by identifying a critical role for autophagy in metastatic breast and melanoma cells in stimulating focal adhesion disassembly and tumor cell motility. This was achieved through autophagic targeting and degradation of PXN, a critical focal adhesion protein that we show interacts directly with LC3B at the phagophore. Significantly in terms of tumorigenesis, this direct protein-protein interaction between PXN and LC3B is strongly enhanced by oncogenic SRC and, indeed, we also showed that functional autophagy is required for SRC-induced migration and invasion by metastatic tumor cells.