Discoidin domain receptor 2 (DDR2) belongs to the family of receptor tyrosine kinases (RTKs) that binds to and is activated by collagen in the extracellular matrix. RTKs are important for the communication of cells with their microenvironment and are involved in the regulation of cell growth, differentiation and metabolism. The DDR2 gene is located on chromosome 1q23.3, and the DDR2 protein is expressed in epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain . Using an exon sequencing assay, DDR2 was first identified as a potential oncogenic target in lung squamous cell cancer (SCC). The authors reported a 3.8% incidence of DDR2 point mutations in lung SCC samples . Depletion of mutant DDR2 using RNA interference in lung SCC cells demonstrated oncogene addiction. In addition, DDR2 has been implicated to exhibits crosstalk with other cell surface receptors such as the integrins and RTKs resulting in diversification of downstream signal transduction networks. Moreover, DDR2 has been shown to function as an adhesion receptor, which is activated by collagen, although there is limited information available on the signaling pathways activated by DDR2 upon collagen engagement. Rather, Payne et al. showed that these signaling events are independent of integrin activation by collagen and are specific to the DDR2 pathway. Recently, DDR2 has been implicated in a number of cancer types to play a role in driving proliferation and metastasis.
Fan Y, Xu Z, Fan J, et al. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer. American Journal of Translational Research. 2016;8(6):2845-2850.