The “Sharp” blade against HIF-mediated metastasis

Amelio, Ivano; Melino, Gerry

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 HIF1? to the proteasome and promotes its O2-indendpendet degradation, counteracting HIF-mediated metastasis. These findings shed light on how HIFs are manipulated during cancer pathogenesis.

• Journal Article Type: Article
• Online Publication Date: Oct 31, 2014
• Publication Date: Dec 15, 2012
• Deposit Date: Apr 1, 2020
• Journal: Cell Cycle
• Print ISSN: 1538-4101
• Electronic ISSN: 1551-4005
• Publisher: Taylor & Francis Open
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 24
• Pages: 4530-4535
• DOI: https://doi.org/10.4161/cc.22820
• Keywords: HIF, Sharp1, hypoxia, metastasis, cancer metabolism, breast cancer, angiogenesis, VHL, p63
• Public URL: https://nottingham-repository.worktribe.com/output/4237312
• Publisher URL: https://www.tandfonline.com/doi/full/10.4161/cc.22820