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 overexpressing Sharp1 or MDA-MB-231 cells depleted of HIF1a and HIF2a (shHIF). Cells were left untreated in normal culturing conditions before harvesting. Samples were then processed for total RNA extraction and hybridization on Affymetrix microarrays. Four biological replicas (A, B, C, D) were used for each of the 4 conditions (1: shGFP, control cells; 2: shHIF cells; 3: Sharp1-overexpressing cells) for a total of 12 samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Montagner M 

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

REPOSITORIES: biostudies-other