Affinage

DCC

Netrin receptor DCC · UniProt P43146

Length
1447 aa
Mass
158.5 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DCC is a single-pass transmembrane immunoglobulin-superfamily receptor for netrin-1 that directs axon guidance, cell motility, and cell survival decisions in the nervous system and epithelium (PMID:8861902). It functions as a dependence receptor: in the absence of netrin-1 it actively induces apoptosis, being cleaved by caspase-3 at Asp1290 and triggering a caspase-9-dependent, mitochondria- and death-receptor-independent caspase cascade through direct association with caspase-3 and caspase-9 and the adaptor DIP13α, a pro-apoptotic output that requires DCC localization to lipid rafts (PMID:9796814, PMID:11248093, PMID:12011067, PMID:16537496). This dependence-receptor activity is physiologically protective — its genetic silencing drives spontaneous and APC-cooperative intestinal tumorigenesis, and loss of netrin-1 in the adult substantia nigra triggers DCC cleavage and dopamine-neuron death (PMID:22158121, PMID:33351190). Netrin-1 binds the fifth fibronectin type III repeat of DCC with 1:1 stoichiometry, an interaction potentiated by cell-autonomous heparan sulfate, and switches DCC to a pro-outgrowth signaling mode (PMID:12810718, PMID:17442818). Ligand engagement recruits the Src-family kinase Fyn, which phosphorylates DCC at Y1418, and assembles intracellular effector complexes including FAK and N-WASP that inhibit RhoA and activate Cdc42/Rac1 to remodel actin into filopodia and processes; netrin-1/DCC also activates PLCγ1 via Src and docks ERK2 at the P1 intracellular domain via a MAPK docking motif (PMID:11817894, PMID:15557120, PMID:19141671, PMID:21070949, PMID:30224412). DCC additionally scaffolds eukaryotic initiation factors and ribosomal subunits to mediate netrin-1-stimulated local protein synthesis, and its surface availability is controlled by PKA-driven translocation from intracellular vesicles and by TRIM9-dependent ubiquitination that gates DCC-FAK coupling and exocytic axon branching (PMID:15044543, PMID:20434207, PMID:28701345). In the adult forebrain and hippocampus DCC sustains Src-dependent NMDAR function, LTP, dendritic spine maintenance, and memory, with distinct pre- and postsynaptic contributions (PMID:23291093, PMID:32264905). DCC abundance and isoform composition are tightly regulated post-transcriptionally by NOVA-dependent alternative splicing, by miR-218 and miR-9, and by ubiquitin-mediated degradation (PMID:27223328, PMID:27773352, PMID:30626732, PMID:32857970).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1996 High

    Established the founding mechanistic identity of DCC by showing it is a functional netrin-1 receptor required for axon outgrowth, answering what ligand DCC transduces.

    Evidence Netrin-1 binding assay and anti-DCC antibody blocking of commissural axon outgrowth in vitro

    PMID:8861902

    Open questions at the time
    • Did not define the binding domain
    • Did not address downstream signaling effectors
  2. 1998 High

    Revealed DCC as a dependence receptor that triggers apoptosis when unliganded, reframing it as an active cell-death effector rather than a passive guidance receptor.

    Evidence Cell-based apoptosis assays with caspase-3 cleavage-site (D1290) mutagenesis

    PMID:9796814

    Open questions at the time
    • Did not identify which caspases execute the cascade
    • Did not establish the subcellular requirement for apoptosis
  3. 2001 Medium

    Defined the apoptotic execution route as a caspase-9/caspase-3 cascade independent of mitochondrial and death-receptor pathways, distinguishing DCC's death mechanism.

    Evidence Reciprocal co-IP of DCC with caspase-3/9 and pathway-inhibitor apoptosis assays

    PMID:11248093

    Open questions at the time
    • Single lab
    • Did not map the caspase-interaction interface on DCC
  4. 2002 Medium

    Connected DCC to the actin machinery by showing netrin-1-dependent activation of Cdc42 and Rac1 drives filopodia and cell spreading, beginning the cytoskeletal effector map.

    Evidence Ectopic DCC expression with dominant-negative Cdc42/Rac1 and GTPase activation assays

    PMID:11817894

    Open questions at the time
    • Did not link GTPase activation to a defined DCC intracellular motif
    • Single cell-line context
  5. 2002 Medium

    Identified DIP13α as an adaptor required for DCC-induced apoptosis, providing a molecular bridge for the dependence-receptor death output.

    Evidence Co-IP, domain-deletion mapping, siRNA knockdown with apoptosis readout

    PMID:12011067

    Open questions at the time
    • Did not show DIP13α links DCC directly to caspases
    • Single lab
  6. 2003 High

    Localized the netrin-1 binding site to the FN5 repeat with 1:1 stoichiometry, defining the receptor-ligand interaction at domain resolution.

    Evidence Soluble netrin fragment pull-down, cross-linking, and stoichiometric analysis

    PMID:12810718

    Open questions at the time
    • Did not provide atomic-resolution structure of the complex
    • Did not address receptor oligomerization on ligand binding
  7. 2004 High

    Showed PKA controls surface delivery of DCC from intracellular vesicles, establishing receptor availability as a regulated node tuning netrin-1 responsiveness.

    Evidence Surface biotinylation, imaging of DCC pools, and pharmacological inhibition of PKA/exocytosis in commissural neurons

    PMID:15044543

    Open questions at the time
    • Did not identify the vesicular trafficking machinery
    • Mechanism linking PKA to DCC vesicles unresolved
  8. 2004 High

    Identified Fyn as the kinase phosphorylating DCC at Y1418 and required for netrin-1-driven outgrowth, defining the proximal tyrosine-kinase signaling step.

    Evidence In vitro Fyn/Src kinase assays, Y1418 mutagenesis, and Fyn-/- commissural neuron explants

    PMID:15557120

    Open questions at the time
    • Did not connect Y1418 phosphorylation to specific downstream effectors
    • Did not address other DCC phosphosites
  9. 2006 Medium

    Demonstrated lipid-raft localization is required for DCC pro-apoptotic activity and caspase-9 recruitment, spatially compartmentalizing the death signal.

    Evidence Lipid raft fractionation, raft disruption, and caspase-9 co-IP with apoptosis assays

    PMID:16537496

    Open questions at the time
    • Did not define raft-targeting sequence in DCC
    • Single lab
  10. 2006 Medium

    Linked DCC to the ERM/cortical actin system via ezrin/merlin binding through a juxtamembrane domain, extending the cytoskeletal interactome.

    Evidence In vitro pull-down, co-IP in COS-1, and adhesion/morphology assays

    PMID:16762451

    Open questions at the time
    • Did not establish netrin-1 dependence of the ezrin interaction
    • Functional role in axon guidance not tested
  11. 2007 High

    Established heparan sulfate as a cell-autonomous co-requirement for netrin-1/DCC signaling, identifying a glycan cofactor for productive receptor output.

    Evidence Conditional Ext1 knockout, axon pathfinding, and DCC signaling readouts in HEK293T

    PMID:17442818

    Open questions at the time
    • Did not resolve whether HS modifies DCC, netrin-1, or the complex geometry
    • Downstream signaling defect mechanism unspecified
  12. 2009 High

    Assembled the pro-outgrowth effector complex (Fyn/FAK/N-WASP) downstream of DCC and showed RhoA inhibition drives process remodeling, mechanistically opposing the dependence-receptor mode.

    Evidence Co-IP of Fyn/FAK/N-WASP with DCC, Fyn-/- oligodendrocytes, RhoA assays, branching assays

    PMID:19141671

    Open questions at the time
    • Did not define stoichiometry or assembly order of the complex
    • Demonstrated in oligodendrocytes; generalization to axons inferred
  13. 2010 High

    Revealed DCC as a scaffold for translation initiation factors and ribosomes mediating netrin-1-stimulated local protein synthesis, expanding DCC function beyond signaling to translational control.

    Evidence Reciprocal co-IP with eIFs and ribosomal subunits, polysome profiling, in situ protein synthesis detection

    PMID:20434207

    Open questions at the time
    • Did not identify mRNAs translated under DCC control
    • Did not map the DCC region binding translation machinery
  14. 2010 High

    Provided structural basis for ERK2 docking on the DCC P1 domain, defining a direct MAPK-receptor coupling in netrin signaling.

    Evidence X-ray crystal structure of ERK2-P1 complex, docking-motif mutagenesis, in vitro kinase assay

    PMID:21070949

    Open questions at the time
    • Did not establish the downstream transcriptional/cytoskeletal output of ERK2-DCC
    • Cellular consequence of docking-motif mutation not tested in vivo
  15. 2011 High

    Placed DCC upstream of Src-dependent NMDAR function required for LTP and memory, extending its role to adult synaptic plasticity.

    Evidence Conditional neuronal DCC knockout, LTP electrophysiology, Src activity assays, NMDAR/Src rescue

    PMID:23291093

    Open questions at the time
    • Did not establish whether DCC-Src signaling at synapses requires netrin-1
    • Molecular link from DCC to Src activation at synapses unresolved
  16. 2011 High

    Demonstrated in vivo that DCC's pro-apoptotic dependence activity is the basis of its tumor-suppressor function, causally linking the death mechanism to cancer.

    Evidence Mouse with genetically silenced DCC pro-apoptotic activity crossed to APC-mutant background, tumor monitoring

    PMID:22158121

    Open questions at the time
    • Did not address whether netrin-1 levels modulate tumor outcome
    • Mechanism of apoptosis silencing in epithelium not detailed
  17. 2014 High

    Identified TRIM9-dependent ubiquitination as a switch gating DCC-FAK coupling and netrin-1-triggered exocytic axon branching, adding PTM control to receptor output.

    Evidence Co-IP, ubiquitination assays, FAK activity assay, exocytosis measurement, branching assays

    PMID:28701345

    Open questions at the time
    • Did not map DCC ubiquitination sites
    • Did not connect ubiquitination state to the dependence-receptor death mode
  18. 2014 Medium

    Identified CBLN4 as a second extracellular DCC ligand competing with netrin-1 at the FN4-6 region, indicating ligand multiplicity at the netrin-binding interface.

    Evidence Extracellular protein microarray screen and radio-ligand competition binding

    PMID:24400119

    Open questions at the time
    • Did not establish CBLN4-evoked DCC signaling output
    • Single lab
  19. 2016 Medium

    Showed NOVA-controlled alternative splicing of Dcc is required for correct DCC isoform production and guidance function, adding splicing as a post-transcriptional regulatory layer.

    Evidence In vivo RNAi, splicing analysis, and rescue by restoring Dcc splicing in Nova knockouts

    PMID:27223328

    Open questions at the time
    • Did not define the functional difference between DCC splice isoforms
    • Single lab
  20. 2016 Medium

    Established miR-218 as a post-transcriptional repressor of DCC whose loss causes stress-vulnerability behavior, linking DCC dosage to affective phenotypes.

    Evidence miRNA-target reporter assay, expression analysis, viral Dcc overexpression in PFC with behavioral readout

    PMID:27773352

    Open questions at the time
    • Did not define the DCC signaling output driving behavioral susceptibility
    • Single lab
  21. 2017 Medium

    Placed DCC under direct negative transcriptional control by Ctip2 in neocortical neurons governing callosal projection identity, adding transcriptional regulation to its dosage control.

    Evidence Genetic epistasis in Satb2/Ctip2 mutants, in situ hybridization, in utero electroporation

    PMID:24739528

    Open questions at the time
    • Did not show direct Ctip2 binding to the Dcc locus
    • Single lab
  22. 2018 High

    Resolved a triangular Draxin/DCC/netrin-1 complex showing Draxin binds DCC Ig domains adjacent to the netrin site, defining how a third extracellular factor shapes netrin guidance.

    Evidence X-ray crystallography and SAXS of Draxin complexes with haptotaxis/fasciculation assays

    PMID:29503192

    Open questions at the time
    • Did not establish intracellular signaling consequences of the ternary complex
    • Stoichiometry in cellular membranes not addressed
  23. 2018 Medium

    Placed PLCγ1 downstream of netrin-1/DCC via Src for actin rearrangement, extending the cytoskeletal effector pathway and tying it to white-matter development.

    Evidence Conditional Plcg1 knockout, PLCγ1 activation assay downstream of DCC, actin assays, brain histology

    PMID:30224412

    Open questions at the time
    • Did not define how PLCγ1 output drives actin changes
    • Single lab
  24. 2019 Medium

    Identified miR-9 as a direct 3'UTR repressor of DCC controlling Schwann cell migration and DRG axon outgrowth, adding another miRNA tuning DCC abundance.

    Evidence 3'UTR reporter assay, expression analysis, migration and axon outgrowth assays

    PMID:30626732

    Open questions at the time
    • Did not address co-regulation with other DCC-targeting miRNAs
    • Single lab
  25. 2020 High

    Demonstrated that netrin-1 withdrawal triggers DCC cleavage and dopamine-neuron loss in the adult substantia nigra, establishing DCC dependence-receptor signaling as a determinant of adult neuron survival relevant to Parkinsonian models.

    Evidence AAV netrin-1 silencing, DCC cleavage Western blot, dopamine-neuron counting, behavior, and recombinant netrin-1 rescue

    PMID:33351190

    Open questions at the time
    • Did not dissect the caspase cascade in dopamine neurons in vivo
    • Did not address whether DIP13α/raft requirements apply here
  26. 2020 High

    Dissected distinct pre- versus postsynaptic DCC contributions to hippocampal plasticity and memory, refining its synaptic role at circuit resolution.

    Evidence Subregion-specific conditional DCC knockouts, LTP electrophysiology, spine morphology, memory tasks, EPSC recordings

    PMID:32264905

    Open questions at the time
    • Did not identify the molecular effectors differing between pre- and postsynaptic compartments
    • Ligand dependence of synaptic DCC roles not resolved
  27. 2020 Medium

    Showed SEL-10/FBW7-mediated ubiquitin-dependent degradation of UNC-40/DCC prunes sex-specific synapses, establishing regulated DCC turnover as a determinant of circuit connectivity.

    Evidence Undegradable unc-40 gain-of-function allele, SEL-10/UNC-40 co-IP, ubiquitination assays, synaptic imaging in C. elegans

    PMID:32857970

    Open questions at the time
    • Conservation of the SEL-10/FBW7 phosphodegron in mammalian DCC not tested
    • C. elegans ortholog study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dependence-receptor death mode and the netrin-1 pro-outgrowth/survival mode are molecularly switched at the level of a single DCC molecule — integrating ligand occupancy, raft localization, ubiquitination, phosphorylation, and oligomerization — remains unresolved.
  • No unified structural model coupling ligand state to caspase recruitment versus effector assembly
  • Whether CBLN4 and Draxin modulate the apoptotic versus signaling switch is unknown
  • DCC ubiquitination sites and their interplay with phosphorylation are uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0048018 receptor ligand activity 2 GO:0045182 translation regulator activity 1
Localization
GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005840 ribosome 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2
Partners
CASP3CASP9EZRFAKFYNMAPK1NTN1WASL

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DCC (Deleted in Colorectal Cancer) encodes a netrin-1 receptor: DCC protein binds netrin-1, is expressed on spinal commissural axons, and an anti-DCC antibody selectively blocks netrin-1-dependent commissural axon outgrowth in vitro. Netrin-1 binding assay, antibody blocking of commissural axon outgrowth in vitro Cell High 8861902
1998 DCC induces apoptosis in the absence of netrin-1 ligand (dependence receptor activity); netrin-1 engagement blocks apoptosis. DCC is a caspase-3 substrate cleaved at Asp1290, and mutation of this cleavage site abolishes DCC's pro-apoptotic effect. Cell-based apoptosis assays, site-directed mutagenesis of caspase-3 cleavage site (D1290), caspase substrate assays Nature High 9796814
2001 DCC drives caspase-3 activation through caspase-9 independently of the mitochondrial pathway (cytochrome c/Apaf-1-independent) and independently of the death receptor/caspase-8 pathway. DCC physically interacts with both caspase-3 and caspase-9. Co-immunoprecipitation of DCC with caspase-3 and caspase-9; cell-based apoptosis assays with pathway inhibitors Proceedings of the National Academy of Sciences of the United States of America Medium 11248093
2002 DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1 in a netrin-1-dependent manner. Dominant-negative Cdc42 blocks netrin-1-induced filopodia increase, and dominant-negative Rac1 blocks cell surface area increase downstream of DCC. Ectopic DCC expression in HEK293T/NG108-15 cells, dominant-negative Cdc42/Rac1 co-expression, GTPase activation assays Molecular and cellular neurosciences Medium 11817894
2002 DIP13α (a protein with PH and PTB domains) interacts with the DCC cytoplasmic domain and mediates DCC-induced apoptosis; co-expression of DCC and DIP13α produces ~5-fold increase in apoptosis, and siRNA knockdown of DIP13α blocks DCC-induced apoptosis. Co-immunoprecipitation, domain-deletion mutants, siRNA knockdown, cell-based apoptosis assay The Journal of biological chemistry Medium 12011067
2003 Netrin-1 binds exclusively to the fifth fibronectin type III (FN5) repeat of DCC with 1:1 stoichiometry. The loop on FN5 previously implicated in heparin binding is actually important for netrin binding; DCC-heparin interactions are mediated indirectly through netrin. Purified soluble netrin fragment pull-down assay, cross-linking experiments, stoichiometric analysis The Journal of biological chemistry High 12810718
2004 PKA activation promotes translocation of DCC from an intracellular vesicular pool to the plasma membrane in embryonic spinal commissural neurons, selectively increasing cell-surface DCC and enhancing axon outgrowth in response to netrin-1. Inhibiting adenylate cyclase, PKA, or exocytosis blocks DCC translocation. Cell surface biotinylation, immunofluorescence of intracellular vs. plasma membrane DCC pools, pharmacological inhibition of PKA and exocytosis The Journal of neuroscience High 15044543
2004 Fyn (Src family kinase), but not Src, phosphorylates the DCC intracellular domain in vitro; DCC is phosphorylated on tyrosine in vivo upon netrin-1 stimulation. Y1418 is crucial for DCC axon outgrowth function. DCC phosphorylation and netrin-1-induced axon outgrowth are impaired in Fyn-/- neurons. In vitro kinase assay with Fyn/Src on DCC intracellular domain, site-directed mutagenesis (Y1418), Fyn-/- mouse commissural neuron explants The Journal of cell biology High 15557120
2006 DCC localization to lipid rafts is required for its pro-apoptotic (dependence receptor) activity in both immortalized cells and primary neurons. Disruption of lipid rafts inhibits the interaction of caspase-9 with DCC. Lipid raft fractionation, pharmacological disruption of lipid rafts, co-immunoprecipitation of caspase-9 with DCC, cell-based apoptosis assays Proceedings of the National Academy of Sciences of the United States of America Medium 16537496
2006 DCC associates with ezrin (and merlin) via a juxtamembrane ERM-binding domain; this interaction was demonstrated by in vitro pull-down of the DCC cytoplasmic domain with ezrin N-terminal region and confirmed by co-immunoprecipitation in COS-1 cells. DCC expression alters actin cytoskeleton organization and cell adhesion properties. In vitro pull-down assay, co-immunoprecipitation in transfected COS-1 cells, cell morphology and adhesion assays in DCC-transfected HT-29 cells European journal of cell biology Medium 16762451
2007 Cell-autonomous expression of heparan sulfate (HS) by commissural neurons is required for netrin-1/DCC signaling. Ext1 ablation (eliminating HS synthesis) in dorsal spinal cord neurons causes commissural axon guidance defects similar to netrin-1/DCC loss-of-function. Intracellular signaling downstream of netrin-1/DCC is defective in Ext1-deficient neurons and in DCC-transfected cells from which HS was removed. Conditional Ext1 knockout (Wnt1-Cre), commissural axon pathfinding analysis, explant outgrowth assay, DCC signaling readouts in HEK293T cells The Journal of neuroscience High 17442818
2009 Netrin-1 binding to Dcc on mature oligodendrocytes recruits Fyn to a complex with the Dcc intracellular domain that includes FAK and N-WASP, resulting in RhoA inhibition and promoting process remodeling. Fyn kinase (Src family) activity is required downstream of netrin-1-dependent process extension; Fyn-/- oligodendrocytes fail to branch in response to netrin-1. Co-immunoprecipitation of Fyn/FAK/N-WASP with Dcc intracellular domain, Fyn-/- mouse oligodendrocytes, RhoA activity assays, in vitro process branching assays Development High 19141671
2010 DCC forms a binding complex with multiple translation components including eukaryotic initiation factors, ribosomal large and small subunits, and monosomes. Netrin-1 promotes DCC-mediated translation and causes dissociation of translation components from DCC. DCC colocalizes with translation machinery in neuronal axons and dendrites. Co-immunoprecipitation of DCC with translation initiation factors and ribosomal subunits, polysome profiling, in situ detection of newly synthesized protein, netrin-1 stimulation assays Cell High 20434207
2010 ERK2 (MAPK) directly interacts with the DCC intracellular P1 domain via a MAPK docking motif. Crystal structure of ERK2-P1 domain complex reveals physical positioning of DCC phosphorylation sites near the kinase active site. The docking interaction is essential for ERK2-mediated phosphorylation of DCC. Crystal structure (X-ray crystallography) of ERK2-DCC P1 complex, mutagenesis of docking motif, in vitro kinase phosphorylation assay Structure High 21070949
2011 DCC deletion from neurons in the adult forebrain results in loss of LTP, shorter dendritic spines, and impaired spatial/recognition memory. DCC deletion severely reduces Src activation; enhancing NMDAR function or activating Src rescues LTP in DCC-null neurons, placing DCC upstream of Src-dependent NMDAR activation required for LTP. Conditional neuron-specific DCC knockout, LTP electrophysiology, Src kinase activity assay, NMDAR function rescue experiments, dendritic spine morphology analysis Cell reports High 23291093
2011 Genetic silencing of DCC's pro-apoptotic activity in mice leads to spontaneous intestinal neoplasia and increases number and aggressiveness of intestinal tumors in APC-mutant background, demonstrating that DCC suppresses tumor progression via its dependence receptor (pro-apoptotic) activity. Transgenic mouse model with silenced DCC pro-apoptotic activity, tumor development monitoring, APC-mutant cross Nature High 22158121
2014 TRIM9-dependent ubiquitination of DCC blocks DCC interaction with FAK and prevents FAK phosphorylation. Upon netrin-1 stimulation, TRIM9 promotes DCC multimerization but reduces DCC ubiquitination, enabling FAK-DCC interaction and FAK activation, which then promotes exocytic vesicle fusion and axon branching. Co-immunoprecipitation of DCC-FAK, ubiquitination assays, FAK kinase activity assay, exocytosis frequency measurement, in vitro and in vivo axon branching assays Molecular biology of the cell High 28701345
2014 Cerebellin-4 (CBLN4) is a bona fide extracellular ligand of DCC, binding within the membrane-proximal fibronectin type III domains (FN4-6) of DCC, overlapping with the netrin-1 binding site. Netrin-1 competes with CBLN4 for DCC binding with ~5-fold higher affinity. CBLN4 also binds neogenin-1 with lower affinity than DCC. Extracellular protein microarray interaction screen, immunofluorescence, radio-ligand binding competition assay PloS one Medium 24400119
2016 NOVA RNA-binding proteins regulate alternative splicing of Dcc mRNA; Nova deficiency disrupts DCC splice variant production. Restoring correct Dcc splicing in Nova knockouts rescues commissural neuron migration, axon outgrowth, and axon guidance defects. In vivo RNAi screen in dorsal spinal cord, splicing analysis, rescue by restoring Dcc splicing in Nova knockout eLife Medium 27223328
2016 miR-218 acts as a posttranscriptional repressor of DCC in prefrontal cortex pyramidal neurons. Exaggerated DCC expression (with reduced miR-218) in PFC leads to vulnerability to stress-induced social avoidance and anhedonia. Upregulation of Dcc in PFC pyramidal neurons causes susceptibility to depression-like behaviors. miRNA-target reporter assay, in vitro and in vivo miR-218/DCC expression analysis, viral-mediated Dcc overexpression in mouse PFC with behavioral readout Biological psychiatry Medium 27773352
2017 Unc5C and DCC expression are under direct negative transcriptional regulation by Satb2 and Ctip2 respectively in neocortical neurons. Netrin1-Unc5C/DCC interaction controls interhemispheric (callosal) projections in deep-layer neurons. Genetic epistasis (Satb2 and Ctip2 mutant mice), in situ hybridization, in utero electroporation Nature communications Medium 24739528
2018 Crystal/solution structures of Draxin/DCC and Draxin/Netrin-1 complexes reveal: Draxin interacts with DCC through N-terminal four immunoglobulin domains, and with Netrin-1 through its EGF-3 domain. Netrin-1 and DCC bind adjacent sites on Draxin, forming a triangular complex. This arrangement affects Netrin-mediated haptotaxis and axon fasciculation. X-ray crystallography and SAXS solution structures of Draxin/DCC and Draxin/Netrin-1 complexes, functional haptotaxis and fasciculation assays Neuron High 29503192
2018 Netrin-1/DCC activates PLCγ1 through Src kinase to induce actin cytoskeleton rearrangement. Neuronal progenitor-specific knockout of Plcg1 causes axon guidance defects and white matter structural alterations, placing PLCγ1 downstream of netrin-1/DCC signaling. Conditional Plcg1 knockout in neuronal progenitors, PLCγ1 activation assay downstream of DCC, actin rearrangement assays, brain structural MRI/histology EMBO reports Medium 30224412
2019 miR-9 directly targets Dcc mRNA via its 3′-UTR, represses DCC expression, and suppresses Schwann cell migration. let-7 targets Netrin-1. miR-9-mediated downregulation of DCC reduces axon outgrowth in dorsal root ganglion neurons. qRT-PCR, reporter gene (3′-UTR) assay, biochemical expression analysis, Schwann cell migration assay, DRG axon outgrowth assay The Journal of biological chemistry Medium 30626732
2020 Silencing netrin-1 in the adult mouse substantia nigra induces DCC cleavage and significant loss of dopamine neurons, producing motor deficits. Overexpression or brain administration of recombinant netrin-1 is neuroprotective and neurorestorative in mouse/rat PD models, demonstrating that netrin-1/DCC signaling governs adult dopamine neuron survival. AAV-mediated netrin-1 silencing in substantia nigra, DCC cleavage Western blot, dopamine neuron stereological counting, behavioral motor assays, pharmacological netrin-1 administration in PD models The EMBO journal High 33351190
2020 Pre- and postsynaptic DCC contribute distinctly to hippocampal synaptic plasticity: DCC loss from CA1 postsynaptic neurons impairs spatial memory, alters dendritic spine morphology, and reduces postsynaptic adaptor/signaling proteins (but LTP remains intact), while DCC loss from CA3 presynaptic neurons impairs LTP at Schaffer collateral synapses and novel object recognition without altering CA1 intrinsic properties. Hippocampal subregion-specific conditional DCC deletion, LTP electrophysiology, dendritic spine morphology, behavioral memory tasks, electrophysiological recording of spontaneous EPSCs Molecular brain High 32264905
2020 In C. elegans, the E3 ubiquitin ligase SEL-10/FBW7 binds a phosphodegron site on UNC-40/DCC and promotes its ubiquitin-mediated degradation at synapses of one sex (but not the other), thereby pruning sex-specific synaptic connections. An undegradable unc-40 gain-of-function allele retains synapses in both sexes, establishing that local protein degradation of UNC-40/DCC controls sexually dimorphic circuit connectivity. Genetic gain-of-function (undegradable unc-40 allele), co-immunoprecipitation (SEL-10/UNC-40), ubiquitination assays, synaptic connectivity imaging Current biology Medium 32857970

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 874 8861902
1998 The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis. Nature 347 9796814
1994 The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics 222 8188295
2010 Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation. Cell 195 20434207
1994 The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes & development 179 7926722
2001 The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation. Proceedings of the National Academy of Sciences of the United States of America 168 11248093
2002 The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1. Molecular and cellular neurosciences 160 11817894
2003 Netrins and DCC in the guidance of migrating neural crest-derived cells in the developing bowel and pancreas. Developmental biology 153 12798294
2016 DCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218. Biological psychiatry 129 27773352
2013 DCC expression by neurons regulates synaptic plasticity in the adult brain. Cell reports 119 23291093
1998 DCC and netrins. Current opinion in cell biology 112 9818171
2011 The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. The Journal of neuroscience : the official journal of the Society for Neuroscience 109 21653843
2004 Protein kinase A activation promotes plasma membrane insertion of DCC from an intracellular pool: A novel mechanism regulating commissural axon extension. The Journal of neuroscience : the official journal of the Society for Neuroscience 109 15044543
1994 Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues. Cancer research 109 8044801
2002 Mediation of the DCC apoptotic signal by DIP13 alpha. The Journal of biological chemistry 105 12011067
2009 Netrin 1 and Dcc regulate oligodendrocyte process branching and membrane extension via Fyn and RhoA. Development (Cambridge, England) 100 19141671
2004 Phosphorylation of DCC by Fyn mediates Netrin-1 signaling in growth cone guidance. The Journal of cell biology 99 15557120
2004 Role of the dependence receptor DCC in colorectal cancer pathogenesis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 97 15310786
1992 Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts. Oncogene 96 1549369
2003 Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin. The Journal of biological chemistry 91 12810718
2019 The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence. Molecular psychiatry 90 31659271
2007 Epigenetic and genetic alterations in Netrin-1 receptors UNC5C and DCC in human colon cancer. Gastroenterology 89 18054557
2011 DCC constrains tumour progression via its dependence receptor activity. Nature 88 22158121
1997 The expression patterns of guidance receptors, DCC and Neogenin, are spatially and temporally distinct throughout mouse embryogenesis. Developmental biology 88 9441666
2011 A novel DCC mutation and genetic heterogeneity in congenital mirror movements. Neurology 72 21242494
1997 Identification and characterization of neogenin, a DCC-related gene. Oncogene 72 9121761
2015 Signaling mechanism of the netrin-1 receptor DCC in axon guidance. Progress in biophysics and molecular biology 69 25881791
2007 Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 17442818
1994 Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas. British journal of cancer 67 8198970
2003 The dependence receptors DCC and UNC5H as a link between neuronal guidance and survival. Biology of the cell 64 14597260
1997 Loss of DCC expression and glioma progression. Cancer research 61 9012460
2014 Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation. Nature communications 59 24739528
2020 Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson's disease features. The EMBO journal 58 33351190
2016 NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord. eLife 57 27223328
1997 Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma. Cancer research 57 9288786
2000 DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination. Oncogene 56 10698524
1999 Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis. Oncology 56 9949300
2020 The Netrin-1/DCC Guidance Cue Pathway as a Molecular Target in Depression: Translational Evidence. Biological psychiatry 55 32593422
2014 Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases. Neurology 54 24808016
1995 DCC: linking tumor suppressor genes and altered cell surface interactions in cancer? Current opinion in genetics & development 54 7749329
2001 Expression of netrin-1 and its receptors DCC and UNC-5H2 after axotomy and during regeneration of adult rat retinal ganglion cells. Experimental neurology 53 11170725
1996 DCC: is there a connection between tumorigenesis and cell guidance molecules? Biochimica et biophysica acta 52 8876630
1992 Persistent expression of the tumor suppressor gene DCC is essential for neuronal differentiation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 52 1419911
1998 Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers. British journal of cancer 51 9472645
2017 DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome. Human mutation 50 29068161
2014 Defining the ligand specificity of the deleted in colorectal cancer (DCC) receptor. PloS one 48 24400119
2002 Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration. Neuroscience 48 11927147
2019 The microRNAs let-7 and miR-9 down-regulate the axon-guidance genes Ntn1 and Dcc during peripheral nerve regeneration. The Journal of biological chemistry 47 30626732
2015 Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. PLoS genetics 44 26641248
2018 Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC. Neuron 43 29503192
2007 Expression of netrin-1 and its receptors DCC and neogenin in rat brain after ischemia. Brain research 43 17574219
2017 TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching. Molecular biology of the cell 41 28701345
2006 The dependence receptor DCC requires lipid raft localization for cell death signaling. Proceedings of the National Academy of Sciences of the United States of America 41 16537496
2019 Netrin Synergizes Signaling and Adhesion through DCC. Trends in biochemical sciences 40 31704057
2020 Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data. Translational psychiatry 39 32184385
2003 Expression of Netrin-1 and its two receptors DCC and UNC5H2 in the developing mouse lung. Gene expression patterns : GEP 38 12799072
2014 Motor neuron cell bodies are actively positioned by Slit/Robo repulsion and Netrin/DCC attraction. Developmental biology 37 25530182
2008 DCC promoter hypermethylation in esophageal squamous cell carcinoma. International journal of cancer 37 18302152
1995 DCC: linking tumour suppressor genes and altered cell surface interactions in cancer? European journal of cancer (Oxford, England : 1990) 37 7576991
2018 DCC/NTN1 complex mutations in patients with congenital hypogonadotropic hypogonadism impair GnRH neuron development. Human molecular genetics 36 29202173
2015 Ontology application and use at the ENCODE DCC. Database : the journal of biological databases and curation 35 25776021
1999 Reduced expression of APC and DCC gene protein in breast cancer. Histopathology 35 10469217
2015 Congenital mirror movements: phenotypes associated with DCC and RAD51 mutations. Journal of the neurological sciences 34 25813273
2011 Neogenin may functionally substitute for Dcc in chicken. PloS one 33 21779375
1995 The deleted in colorectal cancer (DCC) gene: a candidate tumour suppressor gene encoding a cell surface protein with similarity to neural cell adhesion molecules. Cancer surveys 33 7553661
2022 Discovery of vimseltinib (DCC-3014), a highly selective CSF1R switch-control kinase inhibitor, in clinical development for the treatment of Tenosynovial Giant Cell Tumor (TGCT). Bioorganic & medicinal chemistry letters 32 35961460
2018 Netrin-1/DCC-mediated PLCγ1 activation is required for axon guidance and brain structure development. EMBO reports 32 30224412
2006 DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin. European journal of cell biology 32 16762451
2000 Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene. British journal of cancer 32 10646905
1996 The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases. Oncogene 32 8761300
2020 Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus. Molecular brain 31 32264905
2017 Non cell-autonomous role of DCC in the guidance of the corticospinal tract at the midline. Scientific reports 31 28341853
2016 Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression. PloS one 30 27096627
2020 Synaptic Protein Degradation Controls Sexually Dimorphic Circuits through Regulation of DCC/UNC-40. Current biology : CB 28 32857970
2016 ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis. Open biology 28 27248654
2010 Spatio-temporal deleted in colorectal cancer (DCC) and netrin-1 expression in human foetal brain development. Neuropathology and applied neurobiology 27 20609112
2000 The spatial and temporal expression patterns of netrin receptors, DCC and neogenin, in the developing mouse retina. Experimental eye research 27 10843775
2019 Netrin-1 and Its Receptor DCC Are Causally Implicated in Melanoma Progression. Cancer research 26 31806640
2009 Netrin and DCC: axon guidance regulators at the intersection of nervous system development and cancer. Current drug targets 26 19601764
2010 Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase. Structure (London, England : 1993) 25 21070949
2016 Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. EMBO molecular medicine 24 26882243
2007 Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers. Journal of gastrointestinal and liver diseases : JGLD 24 17410283
2001 Localization of the netrin guidance receptor, DCC, in the developing peripheral and enteric nervous systems. Mechanisms of development 24 11335129
2009 Characterization and expression of netrin-1 and its receptors UNC5B and DCC in human placenta. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 23 19826074
2020 Revisiting the role of Dcc in visual system development with a novel eye clearing method. eLife 22 32096760
2019 DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence. Addiction biology 22 31192517
2017 BLU-285, DCC-2618 Show Activity against GIST. Cancer discovery 22 28077435
2000 Aberration of p53 and DCC in gastric and colorectal cancer. Oncology reports 22 10601600
2015 DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity. EMBO reports 21 25947198
2009 Differential roles of Netrin-1 and its receptor DCC in inferior olivary neuron migration. Molecular and cellular neurosciences 21 19409494
2018 Cardio-supportive devices (VRD & DCC device) and patches for advanced heart failure: A review, summary of state of the art and future directions. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 29549728
2018 Mesocorticolimbic Connectivity and Volumetric Alterations in DCC Mutation Carriers. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 29712788
2017 Recurrent DCC gene losses during bird evolution. Scientific reports 20 28240285
2014 The Netrin-1 receptor DCC is a regulator of maladaptive responses to chronic morphine administration. BMC genomics 20 24884839
2013 Cell invasion through basement membrane: The netrin receptor DCC guides the way. Worm 20 24778942
2018 Egr-1 increases angiogenesis in cartilage via binding Netrin-1 receptor DCC promoter. Journal of orthopaedic surgery and research 19 29843768
2016 Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord. Neural development 19 27784329
1995 Decreased expression of DCC mRNA in gastric and colorectal cancer. Surgery today 19 8645930
2023 The Bcr-Abl inhibitor DCC-2036 inhibits necroptosis and ameliorates osteoarthritis by targeting RIPK1 and RIPK3 kinases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 36931029
2014 Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 25249451

Missed literature

Know a paper Affinage missed for DCC? Flag it for the maintainers and the community.

No submissions yet.