Discoidin domain receptors: A promising target in melanoma.
Fiche publication
Date publication
septembre 2019
Journal
Pigment cell & melanoma research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGEAS Jean-Paul
Tous les auteurs :
Reger de Moura C, Battistella M, Sohail A, Caudron A, Feugeas JP, Podgorniak MP, Pages C, Mazouz Dorval S, Marco O, Menashi S, Fridman R, Lebbé C, Mourah S, Jouenne F
Lien Pubmed
Résumé
The discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family that signals in response to collagen and that has been implicated in cancer progression. In the present study, we investigated the expression and role of DDR1 in human melanoma progression. Immunohistochemical staining of human melanoma specimens (n = 52) shows high DDR1 expression in melanoma lesions that correlates with poor prognosis. DDR1 expression was associated with the clinical characteristics of Clark level and ulceration and with BRAF mutations. Downregulation of DDR1 by small interfering RNA (siRNA) in vitro inhibited melanoma cells malignant properties, migration, invasion, and survival in several human melanoma cell lines. A DDR tyrosine kinase inhibitor (DDR1-IN-1) significantly inhibited melanoma cell proliferation in vitro, and ex vivo and in tumor xenografts, underlining the promising potential of DDR1 inhibition in melanoma.
Mots clés
discoidin domain receptor 1, melanoma, prognosis, therapeutic target, tumor progression
Référence
Pigment Cell Melanoma Res. 2019 09;32(5):697-707