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Published on: December 13, 2019
Interplay between αvβ3 integrin and nucleolin regulates human endothelial and glioma cell migration
Marina Koutsioumpa1, Christos Polytarchou, José Courty
1Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece.
The Journal of Biological Chemistry
|November 20, 2012
Summary
Cell surface nucleolin (NCL) localization depends on α(v)β(3) integrin and its phosphorylation. This interaction is crucial for cancer cell migration and suggests NCL antagonists as potential anticancer agents.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Nucleolin (NCL) is a multifunctional protein overexpressed on activated endothelial and tumor cells.
- NCL mediates angiogenic growth factor actions, like pleiotrophin (PTN), and α(v)β(3) integrin is vital for PTN-induced cell migration.
Purpose of the Study:
- To investigate the interplay between nucleolin (NCL) and α(v)β(3) integrin.
- To determine the mechanisms regulating cell surface NCL localization and its role in cell migration.
Main Methods:
- Biochemical assays
- Immunofluorescence microscopy
- Proximity ligation assays
- Genetic manipulation of protein expression
- Analysis of human glioblastoma tissue arrays
Main Results:
- Cell surface NCL localization requires α(v)β(3) integrin expression and β(3) phosphorylation at Tyr(773).
- This localization is dependent on receptor protein-tyrosine phosphatase β/ζ (RPTPβ/ζ), c-Src, and PI3K signaling.
- NCL interacts with α(v)β(3) and RPTPβ/ζ.
- A positive correlation exists between cell surface NCL and α(v)β(3) expression in glioblastoma.
- NCL antagonists inhibited cell migration only in cells expressing α(v)β(3).
Conclusions:
- Cell surface NCL localization is regulated by α(v)β(3) integrin expression and phosphorylation via the RPTPβ/ζ/c-Src pathway.
- Cell surface NCL and α(v)β(3) integrin expression can serve as biomarkers for NCL antagonist efficacy.
- NCL antagonists show potential as anticancer agents targeting α(v)β(3)-expressing tumors.
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