title: The "Sharp" blade against HIF-mediated metastasis.
abstract: Hypoxia-inducible factors (HIFs) control cellular adaptation to oxygen deprivation. Cancer cells engage HIFs to sustain their growth in adverse conditions, thus promoting a cellular reprograming that includes metabolism, proliferation, survival and mobility. HIFs overexpression in human cancer biopsies correlates with high metastasis and mortality. A recent report has elucidated a novel mechanism for HIFs regulation in triple-negative breast cancer. Specifically, the basic helix-loop-helix (bHLH), Sharp-1, serves HIF1α to the proteasome and promotes its O 2-indendpendet degradation, counteracting HIF-mediated metastasis. These findings shed light on how HIFs are manipulated during cancer pathogenesis.
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK.
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D000099162:Endothelial PAS Domain-Containing Protein 1; C422085:BHLHE41 protein, human