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Review
. 2018;12(4):363-377.
doi: 10.1080/19336918.2018.1465156. Epub 2018 Jun 8.

Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer

Elodie Henriet  1   2 , Margaux Sala  1   2 , Aya Abou Hammoud  1   2 , Adjanie Tuariihionoa  1   2 , Julie Di Martino  1   2 , Manon Ros  1   2   3 , Frédéric Saltel  1   2
Affiliations
Review

Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer

Elodie Henriet et al. Cell Adh Migr. 2018.

Abstract

Discoidin domain receptors, DDR1 and DDR2, are two members of collagen receptor family that belong to tyrosine kinase receptor subgroup. Unlike other matrix receptor-like integrins, these collagen receptors have not been extensively studied. However, more and more studies are focusing on their involvement in cancer. These two receptors are present in several subcellular localizations such as intercellular junction or along type I collagen fibers. Consequently, they are involved in multiple cellular functions, for instance, cell cohesion, proliferation, adhesion, migration and invasion. Furthermore, various signaling pathways are associated with these multiple functions. In this review, we highlight and characterize hallmarks of cancer in which DDRs play crucial roles. We discuss recent data from studies that demonstrate the involvement of DDRs in tumor proliferation, cancer mutations, drug resistance, inflammation, neo-angiogenesis and metastasis. DDRs could be potential targets in cancer and we conclude this review by discussing the different ways to inhibits them.

Keywords: STED microscopy; fenestrae; livers sinusoidal endothelial cells (LSEC).

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Figures

Figure 1.
Figure 1.
Different subcellular localization of DDRs in cells. Schematic representation that illustrates different subcellular localizations of DDRs in cells associated with their functions. 1) In A431 cells, DDR1 interacts with E cadherin and the polarity complex Par3/Par6 in order to maintain cell/cell junction. 2) In A375 cells, DDR1 and DDR2 colocalize together along the type I fibrillar collagen. 3) In A375 melanoma cells, on a collagen I matrix, DDR1 co-localizes with Tks5 (a marker of invadosomes). DDR1 activation induces Tuba/Cdc42 pathway leading to linear invadosome formation. 4) In A375 melanoma migrating cells, both DDR1 and DDR2 co-localize with lamellipodia. Some pathways induced by DDR1 activation are represented in this schematic. Scale bar: 5 µM The cells presented in this figure have been transfected by DDR1 tagged with GFP. Anti-DDR2 antibody was purchased from cell signaling (rabbit, 12133S), E-Cadherin antibody was purchased from abcam (mouse, 1416), anti-Tks5 was purchased from Santa Cruz biotechnology (rabbit, sc30122).
Figure 2.
Figure 2.
DDRs contribution in cancer hallmarks. Representative circular diagram of the hallmarks of cancer, adapted from Hanahan and Weinberg, 2011. In the center, a representative confocal image of a melanoma cancer cell (A375) seeded into collagen fibers (grey) and expressing DDR1 (red). The nucleus is in blue. The difference in the front size is related to the reported involvement of one of hte DDR more than the other in the literature.
See this image and copyright information in PMC

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Grants and funding

E. Henriet and M. Sala are supported by a PhD from the Ministère de l'Enseignement Supérieur et de la Recherche. This work has been supported by grants from SIRIC BRIO, ARC, La Ligue Nationale contre le Cancer. F. Saltel and V. Moreau are supported by fundings from Equipe Labellisée, Ligue Nationale contre le Cancer 2016, SIRIC BRIO and INCA, PLBIO15-135 (to FS) and PLBIO2014-182 (to VM).