Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells
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Louis Theret1,2, Albin Jeanne1,2,3, Benoit Langlois1,2, Cathy Hachet1,2, Marion David4, Michel Khrestchatisky5, Jérôme Devy1,2, Emonard Hervé1,2, Sébastien Almagro1,2 and Stéphane Dedieu1,2
1Université de Reims Champagne-Ardenne, UFR Sciences Exactes et Naturelles, Reims, France
2CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France
3SATT Nord, Lille, France
4VECT-HORUS SAS, Faculté de Médecine Secteur Nord, Marseille, France
5Aix Marseille Université, CNRS, NICN, Marseille, France
Stéphane Dedieu, email: [email protected]
Keywords: LRP-1, β1-integrin, cancer, endocytosis, recycling
Received: March 31, 2017 Accepted: July 25, 2017 Published: August 10, 2017
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 β1-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 β1-integrin conformations and identified the extracellular ligand-binding domains II or IV of LRP-1 as sufficient to bind β1-integrin. Using a recombinant β1-integrin, we demonstrated that LRP-1 acts as a regulator of β1-integrin intracellular traffic. Moreover, RAP or LRP-1 blocking antibodies decreased up to 36% the number of β1-integrin-containing endosomes. LRP-1 blockade did not significantly affect the levels of β1-integrin-containing lysosomes while decreasing localization of β1-integrin within Rab-11 positive vesicles. Overall, we identified an original molecular process in which LRP-1 acts as a main regulator of β1-integrin internalization and recycling in thyroid cancer cells.
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