Recombinant Human DCC Protein, CF

Deleted in Colorectal Cancer (DCC) was originally identified as a putative tumor suppressor gene that is down-regulated in more than 70% of colorectal cancers (1). DCC is a type I transmembrane glycoprotein that belongs to the immunoglobulin (Ig) superfamily (2, 3). It contains an extracellular domain (ECD) composed of four Ig-like domains and six fibronectin type III repeats, a transmembrane region, and a cytoplasmic domain (1, 4-6). The ECD of human DCC shares 97% amino acid sequence identity with mouse and rat DCC. In adults, DCC is expressed most abundantly in brain tissue, but it is also expressed at low levels in multiple other tissues (4, 6). DCC is a receptor for Netrin-1 and is important for dopaminergic neuronal precursor migration, axon guidance, and axon arborization (2, 7-10). Binding of DCC by Draxin, at a site distinct from the Netrin-1 binding site, results in the inhibition of neurite outgrowth (11). Signaling downstream of DCC may also be required for the confinement of central axons to the central nervous system (12). DCC regulates apoptosis as a dependence receptor and induces apoptosis in the absence of Netrin-1 binding (13-15). DCC has been shown to inhibit metastasis, and loss of DCC’s apoptotic activity promotes tumorigenesis in mice, providing in vivo evidence that DCC is a tumor suppressor gene (16-18).