Evidence map›Paper›PMID 21640103›Full record

ArticleExperimental cell research2011

Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner.

Colette J Shen, Srivatsan Raghavan, Zhe Xu, Jan D Baranski, Xiang Yu, Michele A Wozniak, Jordan S Miller, Mudit Gupta, Leonard Buckbinder, Christopher S Chen

Abstract read
In one paragraph

Article in Experimental cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Extracellular matrix and its therapeutic potential for cancer treatment.Signal transduction and targeted therapy · 2021
    Review
  9. Article
  10. Review
  11. Article
  12. Matrix stiffening promotes a tumor vasculature phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Differential effects of a soluble or immobilized VEGFR-binding peptide.Integrative biology : quantitative biosciences from nano to macro · 2012
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Colette J ShenDepartment of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA 19104, USA.
Srivatsan Raghavan
Zhe Xu
Jan D Baranski
Xiang Yu
Michele A Wozniak
Jordan S Miller
Mudit Gupta
Leonard Buckbinder
Christopher S Chen
University of Pennsylvania · USPfizer (United States) · US

Funding

REGULATION OF ANGIOGENESIS BY MICROENVIRONMENTAL CUESR01EB000262 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI CHEN, CHRISTOPHER S · 2002 to 2023
$6.2M
Engineering Multicellular Tissue Structure, Function, and VascularizationR01EB008396 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI BHATIA, SANGEETA N., CHEN, CHRISTOPHER S · 2009 to 2018
$5.8M
NIBIB NIH HHS R01 EB000262NIBIB NIH HHS R01 EB008396
6 · The paper itself

Abstract

Angiogenesis is regulated by both soluble growth factors and cellular interactions with the extracellular matrix (ECM). While cell adhesion via integrins has been shown to be required for angiogenesis, the effects of quantitative changes in cell adhesion and spreading against the ECM remain less clear. Here, we show that angiogenic sprouting in natural and engineered three-dimensional matrices exhibited a biphasic response, with peak sprouting when adhesion to the matrix was limited to intermediate levels. Examining changes in global gene expression to determine a genetic basis for this response, we demonstrate a vascular endothelial growth factor (VEGF)-induced upregulation of genes associated with vascular invasion and remodeling when cell adhesion was limited, whereas cells on highly adhesive surfaces upregulated genes associated with proliferation. To explore a mechanistic basis for this effect, we turned to focal adhesion kinase (FAK), a central player in adhesion signaling previously implicated in angiogenesis, and its homologue, proline-rich tyrosine kinase 2 (Pyk2). While FAK signaling had some impact, our results suggested that Pyk2 can regulate both gene expression and endothelial sprouting through its enhanced activation by VEGF in limited adhesion contexts. We also demonstrate decreased sprouting of tissue explants from Pyk2-null mice as compared to wild type mice as further confirmation of the role of Pyk2 in angiogenic sprouting. These results suggest a surprising finding that limited cell adhesion can enhance endothelial responsiveness to VEGF and demonstrate a novel role for Pyk2 in the adhesive regulation of angiogenesis.

Indexed as

Neovascularization, PhysiologicAnimalsCell AdhesionCells, CulturedEndothelial CellsFocal Adhesion Kinase 2Focal Adhesion Protein-Tyrosine KinasesGene Expression RegulationHumansLigandsMiceMice, KnockoutSignal TransductionVascular Endothelial Growth Factor AFocal Adhesion Kinase 2Focal Adhesion Protein-Tyrosine KinasesLigandsVascular Endothelial Growth Factor A

Identifiers

PMID21640103
PMCPMC3123418
OpenAlexW1989151888

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.