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
