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PMID: 18259193 Published · ppublish English Journal Article Review

The role of hypoxia-inducible factors in tumorigenesis.

Cell death and differentiation ·Vol. 15 ·No. 4 ·2008-04-00 ·Pages 678-85

Rankin EB, Giaccia AJ

Abstract

Hypoxia-inducible factors (HIFs) are essential mediators of the cellular oxygen-signaling pathway. They are heterodimeric transcription factors consisting of an oxygen-sensitive alpha subunit (HIF-alpha) and a constitutive beta subunit (HIF-beta) that facilitate both oxygen delivery and adaptation to oxygen deprivation by regulating the expression of genes that control glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation, and apoptosis. In most experimental models, the HIF pathway is a positive regulator of tumor growth as its inhibition often results in tumor suppression. In clinical samples, HIF is found elevated and correlates with poor patient prognosis in a variety of cancers. In summary, HIF regulates multiple aspects of tumorigenesis, including angiogenesis, proliferation, metabolism, metastasis, differentiation, and response to radiation therapy, making it a critical regulator of the malignant phenotype.

MeSH Terms
Adaptation, Physiological Animals Basic Helix-Loop-Helix Transcription Factors/metabolism Cell Differentiation Cell Hypoxia Cell Proliferation Energy Metabolism Humans Hypoxia/genetics,metabolism,pathology Hypoxia-Inducible Factor 1, alpha Subunit/metabolism Neoplasm Invasiveness Neoplasm Metastasis Neoplasms/genetics,metabolism,pathology,radiotherapy Neovascularization, Pathologic/metabolism Oxygen/metabolism Signal Transduction
Chemicals
Basic Helix-Loop-Helix Transcription Factors Hypoxia-Inducible Factor 1, alpha Subunit endothelial PAS domain-containing protein 1 Oxygen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rankin E B
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Giaccia A J
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Article Info
Journal
Cell death and differentiation
Abbr.
Cell Death Differ
ISSN
1350-9047
DOI
10.1038/cdd.2008.21
Published
2008-04-00
Epub
2008-00-15
Pages
678-85
Language
English
Region
England
NLM ID
9437445
PMCID
PMC3050610
Subset
IM
Grants
NCI NIH HHS · P01 CA067166 · United States
NCI NIH HHS · P01 CA067166-12 · United States
NCI NIH HHS · T32 CA009151 · United States
External Links
PubMed source DOI: 10.1038/cdd.2008.21 PMC Full Text View journal details
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