Corrigendum: Discoidin Domain Receptors: Potential Actors and Targets in Cancer

After surgery, radiation therapy (RT) has long been an integral component of cancer care. It is usually employed to locally eradicate tumor cells as well as alter tumor stroma with either curative or palliative intent (Hodge et al., 2012; Kwilas et al., 2012). Therefore, current efforts have been focusing on understanding the molecular, cellular, and systemic processes driving cancer initiation, progression, heterogeneity, and metastatic spread (Ramos and Bentires-Alj, 2015; Semenova et al., 2015). As a major part of the tumor ECM, type I collagen exhibits high density and altered architecture in malignant cancer and is causally linked to tumor formation and metastasis (Ren et al., 2014). Until recently, these effects on tumor cells were exclusively attributed to integrins, a major class of receptors that mediate cell interactions with extracellular matrix components. The identification of the Discoidin Domain Receptor (DDR) family as collagen receptors represents a new paradigm in the regulation of collagen-cell interactions and regulation of tumor progression (Marquez and Olaso, 2014). DDR1 and DDR2 were initially discovered by homology cloning based on their catalytic kinase domains and were orphan receptors until 1997 when Shrivastava and co-workers and Vogel and co-workers, reported that different types of collagen are functional ligands for these receptors (Leitinger, 2014). In contrast with classical growth factor tyrosine kinase receptors such as the epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) which display a rapid and transient activation, DDR1 and DDR2 are unique in that they exhibit remarkably delayed and sustained receptor phosphorylation upon binding to collagen (Iwai et al., 2013). Furthermore, many classical tyrosine kinase receptors (RTKs) undergo negative regulation such as receptor/ligand internalization and subsequent degradation or dephosphorylation by phosphatases (Fu et al., 2013). In addition, they are uniquely positioned to function as sensors for ECM and to regulate a wide range of cell functions such as migration, cell proliferation, cytokine secretion, and ECM homeostasis/remodeling (Borza and Pozzi, 2014).