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

Frontiers in Oncology

Luisa Iommarini¹  Anna Maria Porcelli¹  Giuseppe Gasparre²  Ivana Kurelac² 

[1] Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Bologna, Italy;Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy;

关键词: hypoxia-inducible factor 1 alpha;    cancer;    mitochondria;    oxidative phosphorylation;    electron transport chain;    prolyl hydroxylases;   

DOI  :  10.3389/fonc.2017.00286

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown