title: Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success.
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.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Branco-Price
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Moritz
authors.initials: M
authors.lastname: Schnelle
authors.forename: Colin
authors.initials: C
authors.lastname: Evans
authors.forename: Dörthe M
authors.initials: DM
authors.lastname: Katschinski
authors.forename: Debbie
authors.initials: D
authors.lastname: Liao
authors.forename: Lesley
authors.initials: L
authors.lastname: Ellies
authors.forename: Randall S
authors.initials: RS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia; D042783:Endothelial Cells / Q000473:pathology; D025461:Feedback, Physiological; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse; C467480:vascular endothelial growth factor A, mouse; C496317:Nos2 protein, mouse