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PMID: 15689487 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression.

Molecular biology of the cell ·Vol. 16 ·No. 4 ·2005-04-00 ·Pages 1901-12

Cowden Dahl KD, Robertson SE, Weaver VM, Simon MC

Abstract

Hypoxia-inducible factor (HIF)-deficient placentas exhibit a number of defects, including changes in cell fate adoption, lack of fetal angiogenesis, hypocellularity, and poor invasion into maternal tissue. HIF is a heterodimeric transcription factor consisting of alpha and beta aryl hydrocarbon receptor nuclear translocator or ARNT) subunits. We used undifferentiated trophoblast stem (TS) cells to characterize HIF-dependent adhesion, migration, and invasion. Arnt(-/-) and Hifalpha(-/-) TS cells exhibit reduced adhesion and migration toward vitronectin compared with wild-type cells. Furthermore, this defect is associated with decreased cell surface expression of integrin alphavbeta3 and significantly decreased expression of this integrin in focal adhesions. Because of the importance of adhesion and migration in tumor progression (in addition to placental development), we examined the affect of culturing B16F0 melanoma cells in 1.5% oxygen (O(2)). Culturing B16F0 melanoma cells at 1.5% O(2) resulted in increased alphavbeta3 integrin surface expression and increased adhesion to and migration toward vitronectin. Together, these data suggest that HIF and O(2) tension influence placental invasion and tumor migration by increasing cell surface expression of alphavbeta3 integrin.

MeSH Terms
Animals Aryl Hydrocarbon Receptor Nuclear Translocator Basic Helix-Loop-Helix Transcription Factors Cell Adhesion Cell Hypoxia/physiology Cell Line Cell Movement DNA-Binding Proteins/deficiency,genetics,metabolism Gene Deletion Gene Expression Regulation/genetics Hypoxia-Inducible Factor 1, alpha Subunit Integrin alphaVbeta3/metabolism Melanoma/metabolism,pathology Mice Oxygen/pharmacology Receptors, Aryl Hydrocarbon/deficiency,genetics,metabolism Stem Cells/cytology,metabolism Transcription Factors/deficiency,genetics,metabolism Trophoblasts/cytology,metabolism
Chemicals
Arnt protein, mouse Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins Hypoxia-Inducible Factor 1, alpha Subunit Integrin alphaVbeta3 Receptors, Aryl Hydrocarbon Transcription Factors Aryl Hydrocarbon Receptor Nuclear Translocator endothelial PAS domain-containing protein 1 Oxygen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cowden Dahl Karen D
Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Robertson Sarah E
Weaver Valerie M
Simon M Celeste
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e04-12-1082
Published
2005-04-00
Epub
2005-00-02
Pages
1901-12
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1073670
Subset
IM
Grants
NHLBI NIH HHS · F31 HL010378 · United States
NHLBI NIH HHS · F31 HL10378 · United States
PHS HHS · R01 66331 · United States
External Links
PubMed source DOI: 10.1091/mbc.e04-12-1082 PMC Full Text View journal details
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