AUTHOR=Iommarini Luisa , Porcelli Anna Maria , Gasparre Giuseppe , Kurelac Ivana 

TITLE=Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer

JOURNAL=Frontiers in Oncology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2017.00286

DOI=10.3389/fonc.2017.00286

ISSN=2234-943X

ABSTRACT=<p>Hypoxia-inducible factor 1 alpha (HIF-1α) 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-1α. However, in certain circumstances, HIF-1α 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-1α regulation, focusing in particular on the consequences of mitochondrial respiratory complexes damage on stabilization of this pleiotropic transcription factor.</p>