Multitasking Discoidin Domain Receptors Are Involved in Several and Specific Hallmarks of Cancer

Overview

Journal Cell Adh Migr

Specialty Cell Biology

Date 2018 Apr 28

PMID 29701112

Citations 31

Authors

Elodie Henriet

Margaux Sala

Aya Abou Hammoud

Adjanie Tuariihionoa

Julie Di Martino

Manon Ros

Frederic Saltel

Affiliations

Soon will be listed here.

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.

Citing Articles

Discoid Domain Receptors Signaling in Macrophages-Mediated Diseases.

Ma Y, Gong H, Cheng L, Zhang D Int J Gen Med. 2025; 18:907-926.

PMID: 39990299 PMC: 11847422. DOI: 10.2147/IJGM.S487093.

Therapeutic advances of targeting receptor tyrosine kinases in cancer.

Tomuleasa C, Tigu A, Munteanu R, Moldovan C, Kegyes D, Onaciu A Signal Transduct Target Ther. 2024; 9(1):201.

PMID: 39138146 PMC: 11323831. DOI: 10.1038/s41392-024-01899-w.

Simultaneous inhibition of discoidin domain receptor 1 and integrin αVβ3 radiosensitizes human glioblastoma cells.

Elser M, Vehlow A, Juratli T, Cordes N Am J Cancer Res. 2023; 13(10):4597-4612.

PMID: 37970361 PMC: 10636682.

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity.

Statzer C, Park J, Ewald C Aging Dis. 2023; 14(3):670-693.

PMID: 37191434 PMC: 10187690. DOI: 10.14336/AD.2022.1116.

A case of neonatal osteofibrous dysplasia with novel CDK12 and DDR2 mutations.

Alodaini A, Abusultan A, Altarooti N, Aldossari A, Hegazi T, Alomran A Bone Rep. 2023; 18:101666.

PMID: 36875508 PMC: 9982453. DOI: 10.1016/j.bonr.2023.101666.

References

Shen Q, Cicinnati V, Zhang X, Iacob S, Weber F, Sotiropoulos G . Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion. Mol Cancer. 2010; 9:227. PMC: 2939569. DOI: 10.1186/1476-4598-9-227. View

Hou G, Vogel W, Bendeck M . The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair. J Clin Invest. 2001; 107(6):727-35. PMC: 208942. DOI: 10.1172/JCI10720. View

Levental K, Yu H, Kass L, Lakins J, Egeblad M, Erler J . Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009; 139(5):891-906. PMC: 2788004. DOI: 10.1016/j.cell.2009.10.027. View

Davies H, Hunter C, Smith R, Stephens P, Greenman C, Bignell G . Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res. 2005; 65(17):7591-5. DOI: 10.1158/0008-5472.CAN-05-1855. View

Ezzoukhry Z, Henriet E, Piquet L, Boye K, Bioulac-Sage P, Balabaud C . TGF-β1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking. Eur J Cell Biol. 2016; 95(11):503-512. DOI: 10.1016/j.ejcb.2016.09.003. View

Lu Q, Chen W, Peng J, Xu Y, Cai Q, Feng G . Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells. Oncol Lett. 2016; 12(5):3598-3608. PMC: 5104140. DOI: 10.3892/ol.2016.5088. View

Das S, Ongusaha P, Yang Y, Park J, Aaronson S, Lee S . Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation. Cancer Res. 2006; 66(16):8123-30. DOI: 10.1158/0008-5472.CAN-06-1215. View

Chung V, Tan T, Huang R, Lai H, Huang R . Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer. Gene. 2017; 635:9-15. DOI: 10.1016/j.gene.2017.09.001. View

Badiola I, Villace P, Basaldua I, Olaso E . Downregulation of discoidin domain receptor 2 in A375 human melanoma cells reduces its experimental liver metastasis ability. Oncol Rep. 2011; 26(4):971-8. DOI: 10.3892/or.2011.1356. View

10.

Yoshida D, Teramoto A . Enhancement of pituitary adenoma cell invasion and adhesion is mediated by discoidin domain receptor-1. J Neurooncol. 2006; 82(1):29-40. DOI: 10.1007/s11060-006-9246-6. View

11.

Li Y, Lu X, Ren X, Ding K . Small molecule discoidin domain receptor kinase inhibitors and potential medical applications. J Med Chem. 2015; 58(8):3287-301. DOI: 10.1021/jm5012319. View

12.

Katanasaka Y, Asai T, Naitou H, Ohashi N, Oku N . Proteomic characterization of angiogenic endothelial cells stimulated with cancer cell-conditioned medium. Biol Pharm Bull. 2007; 30(12):2300-7. DOI: 10.1248/bpb.30.2300. View

13.

Payne L, Huang P . Discoidin domain receptor 2 signaling networks and therapy in lung cancer. J Thorac Oncol. 2014; 9(6):900-4. PMC: 4340565. DOI: 10.1097/JTO.0000000000000164. View

14.

Kamohara H, Yamashiro S, Galligan C, Yoshimura T . Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices. FASEB J. 2001; 15(14):2724-6. DOI: 10.1096/fj.01-0359fje. View

15.

Koh M, Woo Y, Valiathan R, Jung H, Park S, Kim Y . Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition. Int J Cancer. 2014; 136(6):E508-20. PMC: 5033064. DOI: 10.1002/ijc.29154. View

16.

Kadiri M, El Azreq M, Berrazouane S, Boisvert M, Aoudjit F . Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK. J Cell Biochem. 2017; 118(9):2819-2827. DOI: 10.1002/jcb.25932. View

17.

Xu C, Buczkowski K, Zhang Y, Asahina H, Beauchamp E, Terai H . NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination Therapy. Mol Cancer Ther. 2015; 14(10):2382-2389. PMC: 4596771. DOI: 10.1158/1535-7163.MCT-15-0077. View

18.

Kim H, Tan L, Weisberg E, Liu F, Canning P, Choi H . Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol. 2013; 8(10):2145-50. PMC: 3800496. DOI: 10.1021/cb400430t. View

19.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

20.

Lu K, Trcka D, Bendeck M . Collagen stimulates discoidin domain receptor 1-mediated migration of smooth muscle cells through Src. Cardiovasc Pathol. 2010; 20(2):71-6. DOI: 10.1016/j.carpath.2009.12.006. View