Identification of LRP-1 as an endocytosis and recycling receptor for B1-integrin in thyroid cancer cells

Abstract : 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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https://hal.univ-reims.fr/hal-02184520
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Submitted on : Tuesday, July 16, 2019 - 10:25:10 AM
Last modification on : Thursday, October 17, 2019 - 10:08:47 AM

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Louis Theret, Albin Jeanne, Benoît Langlois, Cathy Hachet, Marion David, et al.. Identification of LRP-1 as an endocytosis and recycling receptor for B1-integrin in thyroid cancer cells. Oncotarget, Impact journals, 2017, 8 (45), pp.78614-78632. ⟨10.18632/oncotarget.20201⟩. ⟨hal-02184520⟩

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