MYC Suppresses Cancer Metastasis by Direct Transcriptional Silencing of αv and β3 Integrin Subunits

Over-expression of MYC transforms cells in culture, elicits malignant tumors in experimental animals and is found in many human tumors. We now report the paradoxical finding that this powerful oncogene can also act as a suppressor of cell motility, invasiveness and metastasis. Overexpression of MYC stimulated proliferation of breast cancer cells both in culture and in vivo as expected, but inhibited motility and invasiveness in culture, and lung and liver metastases in xenografted tumors. We show further that MYC represses transcription of both subunits of αvβ3 integrin, and that exogenous expression of β3 integrin in human breast cancer cells that do not express this integrin rescues invasiveness and migration when MYC is downregulated. These data uncover an unexpected function of MYC, provide an explanation for the hitherto puzzling literature on the relationship between MYC and metastasis and reveal a variable that should influence the development of therapeutics that target MYC.