Interplay between αvβ3 Integrin and Nucleolin Regulates Human Endothelial and Glioma Cell Migration

Koutsioumpa, MarinaDepartment of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece (författare)

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.

Polytarchou, ChristosDepartment of Cancer Immunology & AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA (författare)
Courty, JoséLaboratoire CRRET, Universite Paris Est Creteil Val de Marne, avenue du General de Gaulle, 94010 Creteil Cedex, France (författare)
Zhang, YueSino-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 (författare)
Kieffer, NellySino-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 (författare)
Mikelis, ConstantinosDepartment of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece (författare)
Skandalis, Spyros SUppsala universitet,Ludwiginstitutet för cancerforskning (författare)
Hellman, UlfUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)ulfhm (författare)
Iliopoulos, DimitriosDepartment of Cancer Immunology & AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA (författare)
Papadimitriou, EvangeliaDepartment of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Greece (författare)
Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, GreeceDepartment of Cancer Immunology & AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA (creator_code:org_t)

Av författaren/redakt...: Koutsioumpa, Mar ...; Polytarchou, Chr ...; Courty, José; Zhang, Yue; Kieffer, Nelly; Mikelis, Constan ...; visa fler...; Skandalis, Spyro ...; Hellman, Ulf; Iliopoulos, Dimi ...; Papadimitriou, E ...; visa färre...

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