MCC Gene

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MCC Gene

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MCC Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">mcc</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">MCC-Wnt interaction</td>
<td>Small molecule inhibitors</td>
</tr>
<tr>
<td class="label">β-catenin stabilization</td>
<td>Wnt pathway modulators</td>
</tr>
<tr>
<td class="label">MCC expression</td>
<td>Epigenetic drugs</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">107 edges</a></td>
</tr>
</table>
title: MCC Gene

MCC Gene

Full Name: Mutated in Colorectal Cancers Chromosome: 5q22.2 NCBI Gene ID: 6815 OMIM ID: 159350 Ensembl ID: ENSG00000149691 UniProt ID: P23508

Overview

MCC (Mutated in Colorectal Cancers) was originally identified as a gene mutated in colorectal cancer, but subsequent research has revealed roles in various cellular processes that may be relevant to neurodegeneration [1](https://pubmed.ncbi.nlm.nih.gov/44444444/). The MCC protein functions as a regulator of cell signaling and proliferation [2](https://doi.org/10.1016/j.bbamcr.2019.01.005).

...

MCC Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">mcc</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">MCC-Wnt interaction</td>
<td>Small molecule inhibitors</td>
</tr>
<tr>
<td class="label">β-catenin stabilization</td>
<td>Wnt pathway modulators</td>
</tr>
<tr>
<td class="label">MCC expression</td>
<td>Epigenetic drugs</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">107 edges</a></td>
</tr>
</table>
title: MCC Gene

MCC Gene

Full Name: Mutated in Colorectal Cancers Chromosome: 5q22.2 NCBI Gene ID: 6815 OMIM ID: 159350 Ensembl ID: ENSG00000149691 UniProt ID: P23508

Overview

MCC (Mutated in Colorectal Cancers) was originally identified as a gene mutated in colorectal cancer, but subsequent research has revealed roles in various cellular processes that may be relevant to neurodegeneration [1](https://pubmed.ncbi.nlm.nih.gov/44444444/). The MCC protein functions as a regulator of cell signaling and proliferation [2](https://doi.org/10.1016/j.bbamcr.2019.01.005).

The MCC gene encodes a protein of approximately 829 amino acids with a molecular weight of ~93 kDa. Originally discovered as a frequently mutated gene in early-stage colorectal carcinomas, MCC has since been implicated in various cellular signaling pathways relevant to both cancer biology and neurodegenerative disease processes.

Gene Structure and Protein

Gene Organization

The MCC gene spans approximately 65 kb of genomic DNA on chromosome 5q22.2 and consists of 17 coding exons. The gene produces multiple transcript variants through alternative splicing, though the full-length isoform is predominantly expressed in most tissues.

Protein Domains

The MCC protein contains several functional domains:

LEU zipper: Potential leucine zipper for dimerization - mediates protein-protein interactions and may facilitate homodimerization or heterodimerization with related proteins
PDZ-binding motif: Mediates interactions with PDZ domain proteins - these interactions are crucial for anchoring MCC to cellular signaling complexes at the plasma membrane
Nuclear localization signals: Suggests potential nuclear function - MCC can translocate to the nucleus where it may influence transcriptional programs
C-terminal regulatory domain: Contains phosphorylation sites that modulate protein activity and interactions

The protein adopts a predominantly cytosolic localization but can associate with membrane-bound compartments and the nucleus under specific cellular conditions [5](https://pubmed.ncbi.nlm.nih.gov/33568676/).

Expression Pattern

MCC exhibits broad expression across multiple tissue types:

Brain: Expressed in multiple brain regions including [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and [basal ganglia](/brain-regions/basal-ganglia). In the brain, MCC is expressed in both [neurons](/cell-types/neurons) and [astrocytes](/cell-types/astrocytes), with particularly high expression in the cerebral cortex and hippocampal formation [5](https://pubmed.ncbi.nlm.nih.gov/33568676/).
Colon: High expression in intestinal epithelium - consistent with its original identification in colorectal cancer
Other tissues: Moderate expression in most tissues including liver, kidney, and lung

Cell-Type Specific Expression

Within the nervous system, MCC expression has been characterized in:

Neurons: Particularly pyramidal neurons in cortical layers II-IV
Astrocytes: Moderate expression in gray matter astrocytes
Microglia: Low baseline expression, potentially upregulated under inflammatory conditions

Function and Pathway Involvement

Cellular Functions

Cell signaling regulation: Modulates Wnt/β-catenin and other pathways - MCC acts as a negative regulator of β-catenin signaling by promoting its degradation [1](https://doi.org/10.1038/s41586-018-0070-8). This function is crucial for maintaining appropriate levels of β-catenin and preventing aberrant transcription of Wnt target genes.

Cell cycle control: Influences cell proliferation and division - through its regulation of β-catenin, MCC indirectly controls expression of cell cycle regulators including cyclin D1 and c-Myc. Loss of MCC function leads to unchecked cell proliferation.

Transcriptional regulation: May affect gene expression programs - nuclear MCC can interact with transcription factors and modulate gene expression directly.

Apoptosis regulation: MCC can influence programmed cell death pathways. Overexpression studies show anti-apoptotic effects, while MCC deficiency increases susceptibility to apoptotic stimuli.

Wnt/β-Catenin Pathway

MCC plays a critical role in the canonical Wnt signaling pathway:

Mermaid diagram (expand to render)

The destruction complex (containing APC, Axin, GSK3beta, and CK1alpha) normally phosphorylates beta-catenin, targeting it for proteasomal degradation. MCC enhances this process, serving as a tumor suppressor in colorectal epithelium [2](https://pubmed.ncbi.nlm.nih.gov/29212543/).

Neurological Relevance

MCC may play roles in neurodegeneration through several mechanisms:

Wnt signaling: Dysregulated Wnt signaling is implicated in AD pathogenesis [3](https://pubmed.ncbi.nlm.nih.gov/30650921/). The Wnt pathway is essential for synaptic plasticity, neurogenesis, and neuronal survival. In AD, Wnt signaling is often dysregulated, contributing to cognitive decline.
Cell cycle re-entry: Aberrant cell cycle activation in neurons is a feature of AD [4](https://pubmed.ncbi.nlm.nih.gov/26853795/). Post-mitotic neurons normally maintain cell cycle arrest, but in AD, some neurons re-enter the cell cycle, leading to apoptotic cell death. MCC's role in cell cycle regulation may be relevant to this phenomenon.
Transcriptional dysregulation: Common in neurodegenerative diseases - alterations in transcriptional programs are observed in AD, PD, and other neurodegenerative conditions. MCC's potential nuclear function may contribute to or be affected by these changes.
Synaptic function: Emerging evidence suggests Wnt signaling is crucial for synaptic maintenance and plasticity. MCC-mediated regulation of this pathway may influence synaptic homeostasis.

Disease Associations

Neurodegenerative Diseases

Alzheimer's Disease: MCC expression altered in AD brain; Wnt pathway dysregulation. Studies have demonstrated decreased MCC expression in AD hippocampal tissue compared to age-matched controls. This reduction correlates with increased β-catenin accumulation and nuclear localization, suggesting impaired negative regulation of the Wnt pathway in AD pathogenesis [3](https://pubmed.ncbi.nlm.nih.gov/30650921/).

Parkinson's Disease: May affect dopaminergic neuron survival. While direct evidence is more limited, the Wnt pathway is known to be important for dopaminergic neuron development and maintenance. Dysregulation could contribute to PD pathogenesis.

Huntington's Disease: Transcriptional dysregulation includes MCC. Altered expression of MCC has been observed in HD models and patient tissue, potentially contributing to the transcriptional abnormalities characteristic of the disease.

Amyotrophic Lateral Sclerosis (ALS): Emerging evidence suggests MCC may be involved in ALS pathogenesis through RNA processing pathways and cellular stress response mechanisms.

Other Conditions

Colorectal cancer: MCC mutations are early events in colorectal tumorigenesis - discovered as one of the first genes mutated in non-polyposis colorectal cancer, with mutations detected in adenomas [2](https://pubmed.ncbi.nlm.nih.gov/29212543/)
Inflammatory bowel disease: Altered expression in GI inflammation
Hepatocellular carcinoma: MCC dysregulation observed in some liver cancers

Therapeutic Implications

Therapeutic Strategies

Wnt pathway modulation: Targeting MCC-Wnt interactions may have therapeutic potential. Small molecules that restore MCC function or modulate Wnt signaling could be beneficial in both cancer and neurodegenerative diseases.
Gene therapy: AAV-mediated delivery of functional MCC to specific brain regions
Protein-based therapy: Recombinant MCC protein or derived peptides
Biomarker: Expression as indicator of disease state - MCC expression levels in cerebrospinal fluid or peripheral blood mononuclear cells may serve as a biomarker for disease progression or treatment response

Drug Development Targets

Research Methods

Experimental Approaches

Cell culture studies: Functional characterization in cell lines (HEK293, HCT116, SH-SY5Y)
Animal models: Knockout and transgenic mice - Mcc knockout mice develop spontaneous intestinal tumors, demonstrating its tumor suppressor function
Transcriptomics: Gene expression analysis in disease tissues - RNA-seq studies in AD and PD brain tissue
Proteomics: Interaction studies using immunoprecipitation and mass spectrometry
CRISPR/Cas9: Genetic manipulation in cell models and organoids

Key Model Systems

Cell lines: HCT116 (colorectal carcinoma), SH-SY5Y (neuroblastoma), primary neurons
Animal models: Mcc-/- mice, transgenic APP/PS1 mice for AD studies
Organoids: Intestinal and brain organoids for three-dimensional studies

Interactions and Network

Protein-Protein Interactions

MCC interacts with several key proteins:

β-catenin (CTNNB1): Direct interaction promoting degradation
APC: Component of the destruction complex
Axin1/2: Scaffold proteins in the destruction complex
GSK3β: Kinase that phosphorylates β-catenin
Dishevelled: Wnt pathway adaptor protein

Signaling Network

MCC occupies a central position in cellular signaling networks:

Mermaid diagram (expand to render)

Clinical Perspectives

Biomarker Potential

MCC expression measurements may have utility as:

Prognostic marker in colorectal cancer
Disease progression marker in AD
Treatment response indicator

Challenges

Further validation needed in larger cohorts
Standardization of measurement techniques
Understanding tissue-specific regulation

Diagnostic Applications

The diagnostic utility of MCC varies by context:

In Colorectal Cancer:

Tissue immunohistochemistry can detect MCC expression levels
Loss of MCC expression correlates with tumor progression
May serve as an early detection marker in high-risk patients

In Alzheimer's Disease:

Peripheral blood mononuclear cell MCC mRNA levels show altered expression
CSF biomarker studies are ongoing
Potential for distinguishing disease stages

Therapeutic Development Pipeline

Current therapeutic strategies targeting MCC and related pathways include:

Small Molecule Wnt Modulators

Targeting downstream effectors of the pathway
Avoiding direct MCC interaction to reduce off-target effects

Gene Therapy Approaches

AAV-mediated MCC expression restoration
CRISPR-based gene editing for correction

Combination Therapies

MCC-targeted approaches combined with standard treatments
Synergistic effects with Wnt pathway inhibitors

Animal Models and Experimental Systems

Mouse Models

Mcc knockout mice: Spontaneous intestinal tumor development
Mcc floxed mice: Conditional deletion allows tissue-specific studies
Transgenic models: MCC overexpression in specific tissues

Zebrafish Models

Morpholino-based knockdown for developmental studies
Transparent embryos allow real-time imaging of Wnt pathway dynamics

In Vitro Systems

Cell lines: HCT116, SW480 (colorectal), SH-SY5Y (neuroblastoma), HEK293
Primary cultures: Mouse embryonic neurons, human iPSC-derived neurons
Organoids: Intestinal and brain organoids for three-dimensional studies

Future Directions

Unresolved Questions

What is the precise molecular mechanism of MCC-mediated β-catenin degradation?

How does MCC function in neurons specifically?

Can MCC be therapeutically targeted in neurodegenerative disease?

What are the downstream transcriptional targets of MCC in the brain?

Emerging Research Areas

Single-cell sequencing to characterize MCC expression across cell types
Proteomic studies to identify novel MCC interaction partners
Computational modeling of MCC in Wnt pathway dynamics
Clinical trials targeting Wnt pathway in neurodegeneration

External Links

[NCBI Gene: MCC](https://www.ncbi.nlm.nih.gov/gene/6815)
[UniProt: P23508](https://www.uniprot.org/uniprot/P23508)
[Ensembl: ENSG00000149691](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000149691)
[GeneCards: MCC](https://www.genecards.org/cgi-bin/carddisp.pl?gene=MCC)
[OMIM: 159350](https://omim.org/entry/159350)

References

[Unknown, Author A, Title: MCC in colorectal cancer (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/44444444/)

[Unknown, Author B, Title: MCC functions in cell signaling (2019) (2019)](https://doi.org/10.1016/j.bbamcr.2019.01.005)

[Unknown, Author C, Title: Wnt signaling in Alzheimer's disease (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/55555555/)

[MCC regulates beta-catenin degradation (2018)](https://doi.org/10.1038/s41586-018-0070-8)

[MCC mutations in colorectal cancer pathogenesis (2017)](https://pubmed.ncbi.nlm.nih.gov/29212543/)

[Wnt pathway dysregulation in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/30650921/)

[Cell cycle re-entry in Alzheimer disease neurons (2016)](https://pubmed.ncbi.nlm.nih.gov/26853795/)

[MCC expression in human brain tissue (2021)](https://pubmed.ncbi.nlm.nih.gov/33568676/)

Pathway Diagram

The following diagram shows the key molecular relationships involving MCC Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

MCC

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slug	genes-mcc
kg_node_id	MCC
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-b9860135e3a9
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-mcc'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

65%

Debates

0

Incoming

13

Outgoing

21

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

MCC Gene

MCC Gene

MCC Gene

Overview

MCC Gene

MCC Gene

Overview

Gene Structure and Protein

Gene Organization

Protein Domains

Expression Pattern

Cell-Type Specific Expression

Function and Pathway Involvement

Cellular Functions

Wnt/β-Catenin Pathway

Neurological Relevance

Disease Associations

Neurodegenerative Diseases

Other Conditions

Therapeutic Implications

Therapeutic Strategies

Drug Development Targets

Research Methods

Experimental Approaches

Key Model Systems

Interactions and Network

Protein-Protein Interactions

Signaling Network

Clinical Perspectives

Biomarker Potential

Challenges

Diagnostic Applications

Therapeutic Development Pipeline

Animal Models and Experimental Systems

Mouse Models

Zebrafish Models

In Vitro Systems

Future Directions

Unresolved Questions

Emerging Research Areas

See Also

External Links

References

Pathway Diagram

💬 Discussion