LRP-1 Promotes Colon Cancer Cell Proliferation in 3D Collagen Matrices by Mediating DDR1 Endocytosis.
Fiche publication
Date publication
janvier 2020
Journal
Frontiers in cell and developmental biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DEDIEU Stéphane, Pr MORJANI Hamid, Dr BENNASROUNE Aline, Dr COLLIN Guillaume, Dr BENNASROUNE Amar
Tous les auteurs :
Le CC, Bennasroune A, Collin G, Hachet C, Lehrter V, Rioult D, Dedieu S, Morjani H, Appert-Collin A
Lien Pubmed
Résumé
Low density lipoprotein receptor related protein-1 (LRP-1) is a large ubiquitous endocytic receptor mediating the clearance of various molecules from the extracellular matrix. Several studies have shown that LRP-1 plays crucial roles during tumorigenesis functioning as a main signal pathway regulator, especially by interacting with other cell-surface receptors. Discoïdin Domain Receptors (DDRs), type I collagen receptors with tyrosine kinase activity, have previously been associated with tumor invasion and aggressiveness in diverse tumor environments. Here, we addressed whether it could exist functional interplays between LRP-1 and DDR1 to control colon carcinoma cell behavior in three-dimensional (3D) collagen matrices. We found that LRP-1 established tight molecular connections with DDR1 at the plasma membrane in colon cancer cells. In this tumor context, we provide evidence that LRP-1 regulates by endocytosis the cell surface levels of DDR1 expression. The LRP-1 mediated endocytosis of DDR1 increased cell proliferation by promoting cell cycle progression into S phase and decreasing apoptosis. In this study, we identified a new molecular way that controls the cell-surface expression of DDR1 and consequently the colon carcinoma cell proliferation and apoptosis and highlighted an additional mechanism by which LRP-1 carries out its sensor activity of the tumor microenvironment.
Mots clés
3D collagen matrix, DDR1, LRP-1, colon cancer cell, proliferation
Référence
Front Cell Dev Biol. 2020 ;8:412