Fiche publication
Date publication
octobre 2017
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DEDIEU Stéphane
,
Dr DEVY Jérôme
,
Dr LANGLOIS Benoît
Tous les auteurs :
Theret L, Jeanne A, Langlois B, Hachet C, David M, Khrestchatisky M, Devy J, Hervé E, Almagro S, Dedieu S
Lien Pubmed
Résumé
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.
Mots clés
LRP-1, cancer, endocytosis, recycling, β1-integrin
Référence
Oncotarget. 2017 Oct 3;8(45):78614-78632
