Discoidin domain receptors: A promising target in melanoma
Coralie Reger de Moura  Maxime Battistella  Anjum Sohail  Anne Caudron  Jean Paul Feugeas  Marie‐Pierre Podgorniak  Cecile Pages  Sarra Mazouz Dorval  Oren Marco … See all authors
First published: 04 July 2019 https://doi.org/10.1111/pcmr.12809
Coralie Reger de Moura and Maxime Battistella: co‐first authors.
Rafael Fridman, Celeste Lebbé, Samia Mourah and Fanélie Jouenne contributed equally to this work: co‐last authors.
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Abstract
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.