Journal
ONCOTARGET
Volume 8, Issue 45, Pages 78614-78632Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20201
Keywords
LRP-1; beta 1-integrin; cancer; endocytosis; recycling
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Funding
- Ligue National Contre Le Cancer (CCIR-Grand Est)
- Centre National de la Recherche Scientifique (CNRS)
- Universite de Reims Champagne-Ardenne
- Ministere de l'Enseignement Superieur et de la Recherche
- French Society for Extracellular Matrix Biology (SFBMEc)
- French Society for Biochemistry and Molecular Biology (SFBBM)
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LRP-1 is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP-1 was reported to control focal adhesion turnover to optimize the adhesion-deadhesion balance to support invasion. To better understand how LRP-1 coordinates cell-extracellular matrix interface, we explored its ability to regulate cell surface integrins in thyroid carcinomas. Using an antibody approach, we demonstrated that beta 1-integrin levels were increased at the plasma membrane under LRP1 silencing or upon RAP treatment, used as LRP-1 antagonist. Our data revealed that LRP-1 binds with both inactive and active beta 1-integrin conformations and identified the extracellular ligand-binding domains II or IV of LRP-1 as sufficient to bind beta 1-integrin. Using a recombinant beta 1-integrin, we demonstrated that LRP-1 acts as a regulator of beta 1-integrin intracellular traffic. Moreover, RAP or LRP-1 blocking antibodies decreased up to 36% the number of beta 1-integrin-containing endosomes. LRP-1 blockade did not significantly affect the levels of beta 1-integrin-containing lysosomes while decreasing localization of beta 1-integrin within Rab-11 positive vesicles. Overall, we identified an original molecular process in which LRP-1 acts as a main regulator of beta 1-integrin internalization and recycling in thyroid cancer cells.
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