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

被引：178

作者：

Iommarini, Luisa ^{[1
]}

Porcelli, Anna Maria ^{[1
]}

Gasparre, Giuseppe ^{[2
]}

Kurelac, Ivana ^{[2
]}

机构：

[1] Univ Bologna, Dipartimento Farm & Biotecnol, Bologna, Italy

[2] Univ Bologna, Dipartimento Sci Med & Chirurg, Bologna, Italy

来源：

FRONTIERS IN ONCOLOGY | 2017年 / 7卷

关键词：

hypoxia-inducible factor 1 alpha; cancer; mitochondria; oxidative phosphorylation; electron transport chain; prolyl hydroxylases; pseudohypoxia; pseudonormoxia; MITOCHONDRIAL RESPIRATORY-CHAIN; ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; FACTOR; 1-ALPHA; TUMOR ANGIOGENESIS; OXIDATIVE-PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVITY; HIF-1-ALPHA EXPRESSION; PROLYL HYDROXYLASES; REDOX REGULATION;

D O I：

10.3389/fonc.2017.00286

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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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页数：9

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