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

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.

Discoidin domain receptors: multitaskers for physiological and pathological processes

“…Along the same lines, Henriet et al highlight the involvement of the DDRs in several and specific hallmarks of cancer. In accordance with other manuscripts of this issue, they describe the role of DDR1 and DDR2 in proliferation, migration, angiogenesis invasion and metastasis [12].…”

Altered Expression of DDR1 in Clear Cell Renal Cell Carcinoma Correlates With miR-199a/b-5p and Patients' Outcome

“…Conflicting results suggesting that DDR1 could either promote or suppress tumor progression, have been disclosed using other types of human cancers (15). An oncogenic role of DDR1 was proposed on the basis of a number of studies that investigated patients' samples and/or cancer cell lines derived from the tumors that arose in the lung (29,30), breast (31,32), ovary (33), pancreas (34), liver (35), prostate (36), large intestine (37), stomach (38), liver (35), pancreas (34), and skin (39).…”

Discoidin domain receptor 2 drives melanoma drug resistance through AXL-dependent phenotype switching

“…DDRs are major players in cancer progression and are associated with a bad prognosis when overexpressed (Henriet et al 2018;Valiathan et al 2012a We demonstrated that DDRs depletion reduced tumoral cell proliferation by reducing MAP kinase pathway activity. To test its clinical relevance, we selected dasatinib, an FDAapproved kinase domain inhibitor in chronic myeloid leukemia (Keating 2017).…”

“…It could be relevant to study DDRs localization in these conditions as DDR1 is known to play a role in cell-cell junctions whereas there has been no reports on this role for DDR2 (Hidalgo-Carcedo et al 2011). Indeed, DDRs can be present in various subcellular compartments associated with several cellular processes involved in cancer progression (Henriet et al 2018). For example, DDR1 and DDR2 co-localize along the same fiber of collagen I (Henriet et al 2018).…”

“…Indeed, DDRs can be present in various subcellular compartments associated with several cellular processes involved in cancer progression (Henriet et al 2018). For example, DDR1 and DDR2 co-localize along the same fiber of collagen I (Henriet et al 2018).…”