Cited by 162Angiogenesis and VEGF in CancerCell Adhesion Molecules ResearchProtease and Inhibitor Mechanisms

Human 1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by 1 1 integrin

Open access
Sudhakar, A.·2005·Journal of Clinical Investigation

Abstract

Human noncollagenous domain 1 of the alpha1 chain of type IV collagen [alpha1(IV)NC1], or arresten, is derived from the carboxy terminal of type IV collagen. It was shown to inhibit angiogenesis and tumor growth in vivo; however, the mechanisms involved are not known. In the present study we demonstrate that human alpha1(IV)NC1 binds to alpha1beta1 integrin, competes with type IV collagen binding to alpha1beta1 integrin, and inhibits migration, proliferation, and tube formation by ECs. Also, alpha1(IV)NC1 pretreatment inhibited FAK/c-Raf/MEK/ERK1/2/p38 MAPK activation in ECs but had no effect on the PI3K/Akt pathway. In contrast, alpha1(IV)NC1 did not affect proliferation, migration, or the activation of FAK/c-Raf/MEK1/2/p38/ERK1 MAPK pathway in alpha1 integrin receptor knockout ECs. Consistent with this, alpha1(IV)NC1 elicited significant antiangiogenic effects and tumor growth inhibition in vivo but failed to do the same in alpha1 integrin receptor knockout mice. This suggests a highly specific, alpha1beta1 integrin-dependent antiangiogenic activity of alpha1(IV)NC1. In addition, alpha1(IV)NC1 inhibited hypoxia-induced expression of hypoxia-inducible factor 1alpha and VEGF in ECs cultured on type IV collagen by inhibiting ERK1/2 and p38 activation. This unravels a hitherto unknown function of human alpha1(IV)NC1 and suggests a critical role for integrins in hypoxia and hypoxia-induced angiogenesis. Collectively, the above data indicate that alpha1(IV)NC1 is a potential therapeutic candidate for targeting tumor angiogenesis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1172/jci24813This paper is marked retracted.

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 70 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Sudhakar, A.
Affiliations
Creighton University (US)
Corresponding author
Sudhakar, A.
Venue
Journal of Clinical Investigation
Published
2005-10-01
Volume
115
Issue
10
Pages
2801-2810
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2130650067
Cited by
162
References
70
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 9 · 2014: 11 · 2013: 10 · 2012: 12
FWCI
5.29
Type
journal article
Language
en
Status
Retracted
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • Flight Attendant Medical Research Institute
  • National Institutes of Health (DK 55001)
  • National Cancer Institute (P30CA016672)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK55000, R01DK055000, DK 62987, R01DK062987, DK-55001, R01DK055001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
alpha1beta1 integrin, antiangiogenic activity, tumor angiogenesis, endothelial cell migration, endothelial cell proliferation, tube formation, PI3K/Akt signaling, hypoxia, hypoxia-inducible factor-1α, vascular endothelial growth factor, tumor growth inhibition
MeSH terms
Enzyme Activation, Fetal Blood, Humans, Neoplasms, Neovascularization, Pathologic, Protein Kinases, Cell Hypoxia, Gene Deletion, Protein Structure, Tertiary, Angiogenesis Inhibitors, MAP Kinase Signaling System, Collagen Type IV, Integrin alpha1beta1, Vascular Endothelial Growth Factor A, Endothelial Cells, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review