TY - JOUR
T1 - Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success
AU - Branco-Price, Cristina
AU - Zhang, Na
AU - Schnelle, Moritz
AU - Evans, Colin
AU - Katschinski, Dörthe M.
AU - Liao, Debbie
AU - Ellies, Lesley
AU - Johnson, Randall S.
PY - 2012/1/17
Y1 - 2012/1/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862909156&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2011.11.017
DO - 10.1016/j.ccr.2011.11.017
M3 - Article
C2 - 22264788
AN - SCOPUS:84862909156
SN - 1535-6108
VL - 21
SP - 52
EP - 65
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -