Hypoxia-inducible factors: cancer progression and clinical translation

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that...

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Bibliographic Details
Published in:The Journal of clinical investigation 2022-06, Vol.132 (11)
Main Authors: Wicks, Elizabeth E, Semenza, Gregg L
Format: Article
Language:English
Subjects:
Blood gases
Cancer
Development and progression
Epithelial-Mesenchymal Transition
Genetic aspects
Health aspects
Homeostasis
Humans
Hypoxia - metabolism
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Neoplastic Stem Cells - pathology
Neovascularization, Pathologic - metabolism
Physiological aspects
Review
Transcription factors
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Summary:Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.
ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/jci159839