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Cancer Cell. 2012 Jan 17;21(1):52-65. doi: 10.1016/j.ccr.2011.11.017.

Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success.

Author information

1
Department of Physiology, Development and Neuroscience, University of Cambridge, UK.

Abstract

The hypoxia inducible transcription factors (HIFs) control many mediators of vascular response, including both angiogenic factors and small molecules such as nitric oxide (NO). In studying how endothelial HIF response itself affects metastasis, we found that loss of HIF-1α in endothelial cells reduces NO synthesis, retards tumor cell migration through endothelial layers, and restricts tumor cell metastasis, and that loss of HIF-2α has in each case the opposite effect. This results from differential regulation of NO homeostasis that in turn regulates vascular endothelial growth factor expression in an NO-dependent feedback loop. These opposing roles for the two HIF factors indicate that both they and endothelial cells regulate metastasis as malignancy progresses.

PMID:
22264788
PMCID:
PMC3334270
DOI:
10.1016/j.ccr.2011.11.017
[Indexed for MEDLINE]
Free PMC Article

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