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

ABSTRACT: 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-1α/HIF-2α proteasomal degradation by serving as HIFs presenting factor to the proteasome independently from oxygen levels and prior ubiquitination. To investigate unbiasedly if Sharp1 is a general inhibitor of HIF induced transcriptional program, we compared the transcriptomic profile of cells either overexpressing Sharp1 or depleted of HIF1a and HIF2a. We collected RNA from control MDA-MB-231 cells (shGFP) or MDA-MB-231 cells o

ORGANISM(S): Homo sapiens

SUBMITTER: Montagner M 

PROVIDER: S-ECPF-GEOD-33950 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other