Identification of LRP-1 As an Endocytosis and Recycling Receptor for Β1-Integrin in Thyroid Cancer Cells
OncoTarget(2017)
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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Key words
LRP-1,beta 1-integrin,cancer,endocytosis,recycling
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