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Oncogene. 2010 Feb 4;29(5):625-34. doi: 10.1038/onc.2009.441. Epub 2009 Nov 30.

Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.

Author information

1
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. gsemenza@jhmi.edu

Abstract

Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared with normal tissue, and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.

PMID:
19946328
PMCID:
PMC2969168
DOI:
10.1038/onc.2009.441
[Indexed for MEDLINE]
Free PMC Article

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