Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells

• Published in: Oncotarget Vol. 8; no. 45; pp. 78614 - 78632
• Main Authors: Theret, Louis, Jeanne, Albin, Langlois, Benoit, Hachet, Cathy, David, Marion, Khrestchatisky, Michel, Devy, Jérôme, Hervé, Emonard, Almagro, Sébastien, Dedieu, Stéphane
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 03-10-2017
• Subjects: Research Paper; endocytosis; recycling; β1-integrin; cancer; LRP-1
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.20201

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
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.