Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner

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dc.citation.firstpage1860en_US
dc.citation.issueNumber13en_US
dc.citation.journalTitleExperimental Cell Researchen_US
dc.citation.lastpage1871en_US
dc.citation.volumeNumber317en_US
dc.contributor.authorShen, Colette J.en_US
dc.contributor.authorRaghavan, Srivatsanen_US
dc.contributor.authorXu, Zheen_US
dc.contributor.authorBaranski, Jan D.en_US
dc.contributor.authorYu, Xiangen_US
dc.contributor.authorWozniak, Michele A.en_US
dc.contributor.authorMiller, Jordan S.en_US
dc.contributor.authorGupta, Muditen_US
dc.contributor.authorBuckbinder, Leonarden_US
dc.contributor.authorChen, Christopher S.en_US
dc.date.accessioned2014-09-22T20:23:28Zen_US
dc.date.available2014-09-22T20:23:28Zen_US
dc.date.issued2011en_US
dc.description.abstractAngiogenesis 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.en_US
dc.identifier.citationShen, Colette J., Raghavan, Srivatsan, Xu, Zhe, et al.. "Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner." <i>Experimental Cell Research,</i> 317, no. 13 (2011) Elsevier: 1860-1871. http://dx.doi.org/10.1016/j.yexcr.2011.05.006.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.yexcr.2011.05.006en_US
dc.identifier.urihttps://hdl.handle.net/1911/77221en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordangiogenesisen_US
dc.subject.keywordcell adhesionen_US
dc.subject.keywordgene expressionen_US
dc.subject.keywordPyk2en_US
dc.subject.keywordVEGFen_US
dc.titleDecreased cell adhesion promotes angiogenesis in a Pyk2-dependent manneren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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