Journal
FRONTIERS IN ONCOLOGY
Volume 7, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2017.00286
Keywords
hypoxia-inducible factor 1 alpha; cancer; mitochondria; oxidative phosphorylation; electron transport chain; prolyl hydroxylases; pseudohypoxia; pseudonormoxia
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Funding
- Associazione Italiana Ricerca sul Cancro (AIRC) [TOUch ME-IG 17387]
- Italian Ministry of Health [DISCO TRIP GR-2013-02356666]
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Hypoxia-inducible factor 1 alpha (HIF-1 alpha) orchestrates cellular adaptation to low oxygen and nutrient-deprived environment and drives progression to malignancy in human solid cancers. Its canonical regulation involves prolyl hydroxylases (PHDs), which in normoxia induce degradation, whereas in hypoxia allow stabilization of HIF-1 alpha. However, in certain circumstances, HIF-1 alpha regulation goes beyond the actual external oxygen levels and involves PHD-independent mechanisms. Here, we gather and discuss the evidence on the non-canonical HIF-1 alpha regulation, focusing in particular on the consequences of mitochondrial respiratory complexes damage on stabilization of this pleiotropic transcription factor.
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