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

Cristina Branco-Price, Na Zhang, Moritz Schnelle, Colin Evans, Dörthe M. Katschinski, Debbie Liao, Lesley Ellies, Randall S. Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticle

94 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)52-65
Number of pages14
JournalCancer Cell
Volume21
Issue number1
DOIs
Publication statusPublished - 17 Jan 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Branco-Price, C., Zhang, N., Schnelle, M., Evans, C., Katschinski, D. M., Liao, D., Ellies, L., & Johnson, R. S. (2012). Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success. Cancer Cell, 21(1), 52-65. https://doi.org/10.1016/j.ccr.2011.11.017