Netrin receptor DCC (DCC)

Netrin receptor DCC (Deleted in colorectal carcinoma) is a transmembrane protein of the immunoglobulin superfamily that functions as both an axon guidance receptor and a tumor suppressor (UniProt P43146). In the nervous system, it mediates Netrin-1-induced attraction, which is essential for proper commissural axon guidance and neuronal migration (PubMed: 29109527). DCC is characterized as a dependence receptor; it triggers apoptosis in the absence of its ligand, Netrin-1, thereby preventing uncontrolled cell survival in environments where Netrin-1 is not present (PubMed: 15107861). In many cancers, including colorectal and breast cancer, the DCC gene is frequently deleted or downregulated, or the ligand Netrin-1 is overexpressed to bypass this apoptotic trigger (PubMed: 24658274). Therapeutic approaches, such as the monoclonal antibody NP137, target the Netrin-1/DCC interaction to restore the pro-apoptotic signaling of DCC in tumor cells (PubMed: 35922511). Beyond oncology, mutations in DCC are linked to neurological conditions such as congenital mirror movements, highlighting its critical role in brain wiring (PubMed: 29109527).

Other names

Deleted in colorectal carcinomaColorectal cancer suppressorImmunoglobulin superfamily DCC subclass member 1IGCC1

DCC functions as a dependence receptor that induces apoptosis via caspase activation when unbound by its ligand, Netrin-1. Therapeutic agents like the monoclonal antibody NP137 block Netrin-1 binding to DCC, thereby re-activating the apoptotic pathway in Netrin-1-overexpressing cancer cells (PubMed: 35922511).