DCC (DCC netrin 1 receptor)
Located on human chromosome 18, the *DCC* (Deleted in Colorectal Cancer) gene encodes a transmembrane receptor that belongs to the immunoglobulin superfamily (IgSF) and is closely related to the netrin-1 receptor family. As a member of this family, DCC possesses immunoglobulin-like domains that facilitate cell-cell recognition and signaling, sharing functional similarities with other members such as neogenin in mediating intercellular interactions. During neural development, DCC plays a pivotal role in axon guidance and neuronal migration by binding to the ligand netrin-1, thereby directing the proper growth of nerve fibers; genetic knockout studies in animal models have confirmed that the absence of DCC results in significant axon guidance defects and neurodevelopmental abnormalities, linking its dysregulation to potential neurodevelopmental disorders. Beyond the nervous system, DCC is expressed in various tissues, including the colon, where it functions as a tumor suppressor. Its activity regulates critical cellular processes, including adhesion, migration, and apoptosis, through the activation of downstream signaling pathways. The gene’s name derives from its frequent deletion in colorectal cancer, a condition where loss-of-function mutations or epigenetic silencing via DNA methylation disrupts normal apoptotic mechanisms and promotes tumorigenesis. Reduced DCC expression is also associated with the progression of other malignancies, such as gastric and pancreatic cancers, where it may facilitate abnormal cell proliferation and metastasis. Conversely, overexpression of DCC has been shown to inhibit tumor cell growth and induce apoptosis, underscoring its protective role against cancer. Furthermore, specific single nucleotide polymorphisms (SNPs) in the *DCC* gene have been implicated in the susceptibility to neuropsychiatric conditions, including schizophrenia, highlighting the gene’s broader relevance in both oncology and neurological health.
Gene Ontology
Subcellular localization of DCC (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for DCC:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 4360 Axon guidance [PATH:hsa04360] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5210 Colorectal cancer [PATH:hsa05210] |
| Name |
|---|
| Apoptosis |
| Axon guidance |
| Caspase activation via extrinsic apoptotic signalig pathway |
| Cell-Cell communication |
| DCC mediated attractive signaling |
| Developmental Biology |
| DSCAM interactions |
| Ligand-independent caspase activation via DCC |
| Netrin mediated repulsion signals |
| Netrin-1 signaling |
| Programmed Cell Death |
| Role of second messengers in netrin-1 signaling |
| Disease | Score | NofPmids | NofSnps | Source |
| MIRROR MOVEMENTS 1 | 0.24 | 0 | 7 | CLINVAR_CTD_human |
| Colorectal Neoplasms | 0.12953026 | 9 | 2 | BeFree_CTD_human_LHGDN |
| Colon Carcinoma | 0.122442977 | 9 | 1 | BeFree_CLINVAR |
| Malignant neoplasm of gallbladder | 0.120542884 | 3 | 1 | BeFree_GWASCAT |
| Obesity | 0.12 | 1 | 1 | GWASCAT |
| Eosinophilic esophagitis | 0.12 | 1 | 1 | GWASCAT |
| melanoma | 0.12 | 1 | 0 | CTD_human |
| Reperfusion Injury | 0.08 | 1 | 0 | RGD |
| Neuritis, Autoimmune, Experimental | 0.08 | 1 | 0 | RGD |
| Colorectal Cancer | 0.014039032 | 44 | 2 | BeFree_GAD |
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