uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Interplay between αvβ3 Integrin and Nucleolin Regulates Human Endothelial and Glioma Cell Migration
Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece.
Department of Cancer Immunology & AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Laboratoire CRRET, Universite Paris Est Creteil Val de Marne, avenue du General de Gaulle, 94010 Creteil Cedex, France.
Sino-French Research Centre for Life Sciences and Genomics, CNRS/LIA124, Rui Jin Hospital, Jiao Tong University Medical School, 197 Rui Jin Er Road, Shanghai 200025, China.
Show others and affiliations
2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 1, 343-354 p.Article in journal (Refereed) Published
Abstract [en]

The multifunctional protein nucleolin (NCL) is overexpressed on the surface of activated endothelial and tumor cells and mediates the stimulatory actions of several angiogenic growth factors, such as pleiotrophin (PTN). Because α(v)β(3) integrin is also required for PTN-induced cell migration, the aim of the present work was to study the interplay between NCL and α(v)β(3) by using biochemical, immunofluorescence, and proximity ligation assays in cells with genetically altered expression of the studied molecules. Interestingly, cell surface NCL localization was detected only in cells expressing α(v)β(3) and depended on the phosphorylation of β(3) at Tyr(773) through receptor protein-tyrosine phosphatase β/ζ (RPTPβ/ζ) and c-Src activation. Downstream of α(v)β(3,) PI3K activity mediated this phenomenon and cell surface NCL was found to interact with both α(v)β(3) and RPTPβ/ζ. Positive correlation of cell surface NCL and α(v)β(3) expression was also observed in human glioblastoma tissue arrays, and inhibition of cell migration by cell surface NCL antagonists was observed only in cells expressing α(v)β(3). Collectively, these data suggest that both expression and β(3) integrin phosphorylation at Tyr(773) determine the cell surface localization of NCL downstream of the RPTPβ/ζ/c-Src signaling cascade and can be used as a biomarker for the use of cell surface NCL antagonists as anticancer agents.

Place, publisher, year, edition, pages
2013. Vol. 288, no 1, 343-354 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-193349DOI: 10.1074/jbc.M112.387076ISI: 000313197200036PubMedID: 23161541OAI: oai:DiVA.org:uu-193349DiVA: diva2:602099
Available from: 2013-01-31 Created: 2013-01-31 Last updated: 2013-02-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Journal of Biological Chemistry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 183 hits
ReferencesLink to record
Permanent link

Direct link