The "Sharp" blade against HIF-mediated metastasis

Cell Cycle. 2012 Dec 15;11(24):4530-5. doi: 10.4161/cc.22820. Epub 2012 Nov 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Breast Neoplasms / complications*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Models, Biological
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology*

Substances

  • BHLHE41 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1
  • endothelial PAS domain-containing protein 1