Discoidin domain receptor tyrosine kinases: new players in cancer progression

• Published in: Cancer and metastasis reviews Vol. 31; no. 1-2; pp. 295 - 321
• Main Authors: Valiathan, Rajeshwari R., Marco, Marta, Leitinger, Birgit, Kleer, Celina G., Fridman, Rafael
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2012; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Collagen; Collagen - metabolism; Development and progression; Discoidin Domain Receptors; Disease Progression; Enzyme Activation; Gene Expression Regulation, Neoplastic; Health aspects; Humans; Medical sciences; Molecular Targeted Therapy; Mutation; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Non-Thematic Review; Oncology; Phenols; Protein Binding; Protein Processing, Post-Translational; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Mitogen - antagonists & inhibitors; Receptors, Mitogen - chemistry; Receptors, Mitogen - genetics; Receptors, Mitogen - metabolism; Signal Transduction; Tumors; Tyrosine; Tyrosine kinase; Signaling; Collagen; Extracellular matrix; Discoidin domain receptor; Metastasis; Cell migration; Enzyme; Transferases; Glycoprotein; trk receptor; Malignant tumor; Cell motility; Signal transduction; Cancerology; Tumor progression; Protein-tyrosine kinase; Cancer; Biological receptor
• ISSN: 0167-7659; 1573-7233; 1573-7233
• DOI: 10.1007/s10555-012-9346-z

Almost all human cancers display dysregulated expression and/or function of one or more receptor tyrosine kinases (RTKs). The strong causative association between altered RTK function and cancer progression has been translated into novel therapeutic strategies that target these cell surface receptors in cancer. Yet, the full spectrum of RTKs that may alter the oncogenic process is not completely understood. Accumulating evidence suggests that a unique set of RTKs known as the discoidin domain receptors (DDRs) play a key role in cancer progression by regulating the interactions of tumor cells with their surrounding collagen matrix. The DDRs are the only RTKs that specifically bind to and are activated by collagen. DDRs control cell and tissue homeostasis by acting as collagen sensors, transducing signals that regulate cell polarity, tissue morphogenesis, and cell differentiation. In cancer, DDRs are hijacked by tumor cells to disrupt normal cell–matrix communication and initiate pro-migratory and pro-invasive programs. Importantly, several cancer types exhibit DDR mutations, which are thought to alter receptor function and contribute to cancer progression. Other evidence suggests that the actions of DDRs in cancer are complex, either promoting or suppressing tumor cell behavior in a DDR type/isoform specific- and context-dependent manner. Thus, there is still a considerable gap in our knowledge of DDR actions in cancer tissues. This review summarizes and discusses the current knowledge on DDR expression and function in cancer. It is hoped that this effort will encourage more research into these poorly understood but unique RTKs, which have the potential of becoming novel therapeutic targets in cancer.