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Pigment Cell Melanoma Res. 2019 Sep;32(5):697-707. doi: 10.1111/pcmr.12809. Epub 2019 Jul 22.

Discoidin domain receptors: A promising target in melanoma.

Author information

1
Inserm, UMR_S976, Université de Paris, Paris, France.
2
Laboratory of Pharmacogenomics, Hôpital Saint-Louis, AP-HP, Paris, France.
3
Department of Pathology, Hôpital Saint-Louis, AP-HP, Paris, France.
4
Université de Paris, Paris, France.
5
Inserm, UMR_S1165, Université de Paris, Paris, France.
6
Department of Pathology and Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA.
7
Inserm, UMR_1137, Université de Paris, Paris, France.
8
Department of Biochemistry, Hôpital Saint-Louis, AP-HP, Paris, France.
9
Department of Dermatology, Hôpital Saint-Louis, AP-HP, Paris, France.
10
Department of Plastic, Reconstructive and Esthetic Surgery, Hôpital Saint-Louis, AP-HP, Paris, France.
11
CNRS-UMR 7149, Laboratory CRRET, Créteil, France.
12
Université Paris 12, Créteil, France.

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.

KEYWORDS:

discoidin domain receptor 1; melanoma; prognosis; therapeutic target; tumor progression

PMID:
31271515
DOI:
10.1111/pcmr.12809
[Indexed for MEDLINE]

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