SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

Triple Negative Breast cancer accounts for some of the most aggressive types of breast cancer. By interrogating clinical datasets, we found that the activities of p63 and Hypoxia-Inducible-Factors (HIFs), two master regulators of the invasive and metastatic cancer cell phenotype are linked in TNBC through the p63-target Sharp1. Mechanistically, Sharp1 promotes HIF-1/HIF-2 proteasomal degradation by serving as HIFs presenting factor to the proteasome independently from oxygen levels and prior ubiquitination.

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Montagner M, Enzo E, Forcato M, Zanconato F, Parenti A, Rampazzo E, Basso G, Leo G, Rosato A, Bicciato S, Cordenonsi M, Piccolo S