Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.
Fiche publication
Date publication
mai 2016
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie, Dr BUACHE Emilie, Pr MORJANI Hamid, Dr EL BTAOURI Hassan
Tous les auteurs :
Saby C, Buache E, Brassart-Pasco S, El Btaouri H, Courageot MP, Van Gulick L, Garnotel R, Jeannesson P, Morjani H
Lien Pubmed
Résumé
Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2.
Référence
Oncotarget. 2016 May;7(18):24908-27