Netrin receptor DCC (DCC) (DCC)

Netrin receptor DCC (Deleted in colorectal cancer) is a transmembrane protein belonging to the immunoglobulin superfamily that serves as a primary receptor for the guidance cue netrin-1 (UniProt: P43146). It is characterized as a "dependence receptor," meaning it triggers two distinct signaling pathways: in the presence of netrin-1, it promotes cell survival, migration, and axon guidance, but in the absence of its ligand, it actively induces apoptosis (PubMed: 10555141). This dual nature allows DCC to function as a tumor suppressor by eliminating cells that stray from areas of ligand availability. Loss of DCC expression, often through allelic deletion of chromosome 18q21, is a frequent event in colorectal, pancreatic, and esophageal cancers, contributing to tumor progression and metastasis (PubMed: 2249552). In the context of drug development, the netrin-1/DCC axis is targeted by inhibitors like NP137, which blocks netrin-1 binding to DCC, thereby unleashing DCC-mediated apoptosis in netrin-1-overexpressing tumors (PubMed: 27525439). Beyond oncology, mutations in DCC are linked to neurological disorders such as congenital mirror movements, highlighting its critical role in the proper wiring of the human nervous system (PubMed: 20436479).

Other names

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

Induction of apoptosis via the dependence receptor mechanism upon ligand deprivation or pharmacological inhibition of ligand binding (PubMed: 10555141).