| 2025 |
UBE2O, a hybrid E2/E3 ubiquitin enzyme, selectively interacts with and ubiquitylates cytosolic CTNNA1 in a phosphorylation-independent manner. Mass spectrometry-based interactome analysis showed that ubiquitylation of CTNNA1 diminishes its interaction with β-catenin while enabling its interaction with vinculin, promoting focal adhesion maturation and cell-to-ECM adhesion during cell spreading. Ubiquitylation thus acts as a molecular switch directing CTNNA1's function toward cell-to-ECM adhesions. |
Co-IP, mass spectrometry-based interactome analysis, ubiquitylation assay, functional cell spreading assay |
EMBO reports |
Medium |
40983751
|
| 2010 |
PTEN–mTOR signaling acts upstream of C/EBPα to control the ratio of p42 to p30 C/EBPα isoforms. p30 C/EBPα binds the CTNNA1 proximal promoter and recruits Polycomb Repressive Complex 2 (PRC2), suppressing CTNNA1 transcription via H3K27me3; p42 C/EBPα binding at the same promoter relieves repression and promotes CTNNA1 expression via H3K4me3. Loss of Pten in mice and zebrafish reduces wild-type C/EBPα and α-catenin protein, inducing myelodysplasia. This defines a conserved PTEN–C/EBPα–CTNNA1 pathway controlling myeloid differentiation. |
Chromatin immunoprecipitation (ChIP), promoter-binding assays, genetic epistasis in mouse and zebrafish loss-of-function models, protein expression analysis |
Blood |
High |
20371743
|
| 2006 |
In HL-60 myeloid leukemia cells (which carry a 5q31 deletion), the retained CTNNA1 allele is epigenetically silenced by promoter methylation and histone deacetylation. Restoration of CTNNA1 expression in these cells resulted in reduced proliferation and apoptotic cell death, establishing a tumor-suppressor function in myeloid cells. |
Methylation analysis, chromatin/histone modification assays, CTNNA1 restoration (gain-of-function) with proliferation and apoptosis readouts in HL-60 cells |
Nature medicine |
High |
17159988
|
| 2009 |
Progressive epigenetic inactivation of CTNNA1 in AML/MDS involves sequential acquisition of repressive histone marks (H3K27me3) at the promoter followed by DNA CpG methylation. The most repressive chromatin state correlates with DNA methylation and is found in advanced (AML) rather than low-risk MDS, indicating stepwise epigenetic silencing during leukemic transformation. |
ChIP for H3K27me3, methylation-specific PCR, gene expression analysis in primary leukemia cells and AML cell lines |
Cancer research |
Medium |
19826047
|
| 1999 |
In the HCT-8 colon cancer cell family (identical to HCT-15, DLD-1, HRT-18), one CTNNA1 allele is constitutively mutated. Spontaneous invasive variants arising due to HMSH6/GTBP mismatch-repair defects carry a mutation or exon skipping in the second CTNNA1 allele, fulfilling Knudsen's two-hit model, establishing CTNNA1 as an invasion-suppressor gene. |
Sequencing of both alleles, genetic analysis of spontaneous invasive variants, mismatch-repair gene context |
Oncogene |
Medium |
10023666
|
| 2021 |
CTNNA1/α-catenin functions as a negative regulator of YAP1–WWTR1/TAZ transcriptional co-factors and is itself an autophagy substrate. α-Catenin levels determine the direction of YAP1–WWTR1/TAZ signaling change after autophagy perturbation: cells with higher CTNNA1 show decreased YAP1–WWTR1/TAZ activity upon autophagy inhibition (because CTNNA1 accumulates and suppresses YAP1–WWTR1/TAZ), while cells with lower CTNNA1 show the opposite. A mathematical model integrating these feedback relationships was experimentally validated. |
Autophagy perturbation experiments, YAP1–WWTR1/TAZ activity assays, mathematical modeling with experimental validation in cell lines with varying CTNNA1 levels |
Autophagy |
Medium |
34036899
|
| 2015 |
Heterozygous missense mutations in CTNNA1 cause butterfly-shaped pigment dystrophy. A Ctnna1 missense mutation in the mouse mutant tvrm5 phenocopies the human disease: RPE cells show increased shedding, large multinucleated cells, pigmentary abnormalities and decreased light-activated responses, demonstrating that CTNNA1 is required for intercellular adhesion and cytokinesis in the retinal pigment epithelium. |
Identification of human missense mutations, chemically-induced mouse mutant characterization (morphological studies, electroretinography), RPE cell analysis |
Nature genetics |
High |
26691986
|
| 2011 |
Bidirectional promoters shared between CTNNA1 and the antisense-oriented LRRTM2 gene drive alternative CTNNA1 transcripts whose translation produces N-terminally truncated CTNNA1 isoforms lacking the β-catenin interaction domain; these isoforms are expressed at high levels in the nervous system. |
Promoter mapping, RT-PCR, protein expression analysis, luciferase reporter assays |
Biochemical and biophysical research communications |
Medium |
21708131
|
| 2013 |
A germline truncating allele of CTNNA1 co-segregates with hereditary diffuse gastric cancer in a CDH1-negative family; the remaining CTNNA1 allele is silenced in invasive tumors and signet ring cells (biallelic inactivation), placing CTNNA1 as a tumor suppressor in the same adherens junction complex as E-cadherin. |
Exome sequencing, Sanger validation, loss-of-heterozygosity analysis, promoter methylation analysis in tumor tissue |
The Journal of pathology |
Medium |
23208944
|
| 2026 |
CTNNA1-truncating transcripts are degraded by nonsense-mediated mRNA decay (NMD) in human gastric cancer cells, resulting in loss of αE-catenin protein. In a humanized Drosophila model, truncating CTNNA1 variants failed to rescue epithelial architecture or viability upon depletion of endogenous Drosophila α-catenin and were associated with increased apoptosis, confirming they are loss-of-function alleles. Non-truncating transcripts retained function. Missense variant p.Asn853Ser (in the M-fragment) showed partial functional loss. |
CRISPR/Cas9 CTNNA1-knockout in gastric cancer cells, NMD analysis (RT-PCR), humanized Drosophila complementation assay (tissue-specific RNAi + CRISPR/Cas9 depletion of endogenous Dα-cat + expression of human WT or mutant αE-catenin), apoptosis readout |
Gut / European journal of human genetics |
High |
40998418 41760782
|
| 2002 |
Alternative splicing of CTNNA1 that was previously reported generates a frameshift rather than an in-frame insert, resulting in a truncated protein. Quantitative RT-PCR showed no relevant expression of this splice variant in any human tissue, cell line, or mouse developmental stage tested, indicating it is not a functionally significant isoform. |
RT-PCR, real-time quantitative RT-PCR across human tissues/cell lines and mouse developmental stages, genomic characterization |
Biochimica et biophysica acta |
Medium |
11997091
|
| 2016 |
The pseudogene CTNNAP1 competes with CTNNA1 for binding to microRNA-141 (miR-141), acting as a competing endogenous RNA (ceRNA). Overexpression of CTNNAP1 reduced miR-141-mediated suppression of CTNNA1, increasing CTNNA1 levels; overexpression of either CTNNAP1 or CTNNA1 inhibited cell proliferation and induced G0/G1 cell cycle arrest in vitro and suppressed tumor growth in vivo. |
ceRNA/miRNA competition assay, overexpression gain-of-function experiments, cell cycle analysis (flow cytometry), xenograft tumor model |
Oncotarget |
Medium |
27487124
|
| 2020 |
Overexpression of CTNNA1 in bladder cancer cell lines (T24, UMUC-2) inhibited cell proliferation, migration, invasion and EMT (increasing E-cadherin, decreasing N-cadherin, Snail, MMP2, MMP9) and promoted apoptosis. GSEA linked CTNNA1 to p53 and apoptosis pathways. CTNNA1 also suppressed tumor growth in a nude mouse xenograft model. |
Overexpression plasmid transfection, CCK-8 proliferation assay, flow cytometry apoptosis assay, wound healing, Transwell invasion, Western blot for EMT markers, GSEA, xenograft mouse model |
Cancer management and research |
Low |
33364826
|