Affinage

AXIN2

Axin-2 · UniProt Q9Y2T1

Length
843 aa
Mass
93.6 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AXIN2 (also called conductin) is a Wnt-responsive scaffold protein that operates as a core negative-feedback regulator of canonical Wnt/β-catenin signaling, with additional roles in centrosome biology, epithelial–mesenchymal transition, and cell-cycle-coupled pathway gating. Transcribed as a direct TCF/LEF target (PMID:11809808), AXIN2 assembles the β-catenin destruction complex with APC and GSK3β to drive β-catenin phosphorylation and proteasomal degradation (PMID:11809809); its polymerization into active condensates is governed by an RGS-domain aggregon that is targeted by Gαi2 and modulated by m6A-dependent mRNA stability through ALKBH5/IGF2BP1 (PMID:31534175, PMID:35115535, PMID:37169182). Beyond canonical destruction-complex activity, AXIN2 localizes to centrosomes via C-Nap1 to phosphorylate β-catenin independently of transcription and maintain centrosome cohesion (PMID:20300119), serves as a nucleocytoplasmic chaperone that exports GSK3β from the nucleus to stabilize Snail1 and promote EMT (PMID:17072303, PMID:22745173), and is itself degraded by APC/C-CDC20 at mitotic exit to allow peak Wnt activity at the G1/S transition (PMID:22322943). Loss-of-function of AXIN2 in mice causes craniosynostosis through derepressed β-catenin–BMP2/4–Osx signaling in osteoprogenitors (PMID:15790973, PMID:19737815).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Establishing that AXIN2 is a direct Wnt/β-catenin transcriptional target—and therefore part of a negative-feedback loop—resolved how the pathway self-limits its own output.

    Evidence TCF/LEF binding-site mutagenesis in reporter constructs, EMSA, and transgenic embryo expression analysis

    PMID:11809808 PMID:11809809

    Open questions at the time
    • Quantitative relationship between Wnt signal strength and AXIN2 induction kinetics was not defined
    • Whether AXIN2 feedback is sufficient to fully reset β-catenin levels or requires AXIN1 cooperation was unresolved
  2. 2005 High

    Knockin rescue experiments showed that AXIN1 and AXIN2 are biochemically interchangeable, attributing their distinct loss-of-function phenotypes to expression-pattern differences rather than unique molecular activities.

    Evidence Axin2 cDNA knocked into the Axin locus in mice; viability and fertility assessed

    PMID:15899843

    Open questions at the time
    • Whether the two paralogs differ in post-translational regulation (e.g., tankyrase sensitivity) was not tested
    • Tissue-specific quantitative expression data were limited
  3. 2005 High

    Loss of Axin2 in mice revealed its essential role in cranial suture patency, linking Wnt/β-catenin derepression to craniosynostosis through osteoprogenitor expansion.

    Evidence Axin2-null mice with craniosynostosis; β-catenin signaling and osteoblast proliferation/differentiation assays

    PMID:15790973

    Open questions at the time
    • Direct target genes mediating osteoprogenitor expansion were not identified
    • Human craniosynostosis patients with AXIN2 mutations were not yet characterized in this study
  4. 2006 High

    Discovery of AXIN2's role as a nucleocytoplasmic chaperone for GSK3β opened a non-canonical function: by exporting GSK3β from the nucleus, AXIN2 stabilizes Snail1 to drive EMT, explaining how Wnt signaling promotes invasion.

    Evidence Knockdown/overexpression in breast cancer cells; nuclear/cytoplasmic fractionation of GSK3β; Snail1 turnover and invasion assays

    PMID:17072303

    Open questions at the time
    • The nuclear export mechanism (NES-dependent vs. passive) was not dissected
    • Whether AXIN1 shares this GSK3β-chaperoning function was not tested
  5. 2009 High

    Genetic epistasis placed BMP2/4 and Osterix downstream of Axin2-regulated β-catenin in osteoblasts, defining a linear Axin2→β-catenin→BMP2/4→Osx pathway for bone formation.

    Evidence Axin2-null mice, β-catenin conditional deletion, BMP2/4 floxed adenoviral Cre deletion, Osx siRNA

    PMID:19737815

    Open questions at the time
    • Whether this pathway operates identically in endochondral versus intramembranous ossification was not resolved
    • Direct transcriptional regulation of BMP2/4 by β-catenin was not shown by ChIP
  6. 2010 High

    Identification of AXIN2 at centrosomes, bound to C-Nap1, demonstrated a transcription-independent role for AXIN2-mediated β-catenin phosphorylation in centrosome cohesion.

    Evidence Reciprocal Co-IP of conductin–C-Nap1; knockdown with centrosome imaging; phospho-β-catenin mutant rescue; actinomycin D controls

    PMID:20300119

    Open questions at the time
    • How centrosomal β-catenin phosphorylation physically links to centrosome linker integrity was unclear
    • Whether AXIN1 is also present at centrosomes was not addressed
  7. 2011 High

    Axin2 was shown to regulate oligodendrocyte progenitor differentiation and CNS remyelination, and pharmacological stabilization of Axin2 (via tankyrase inhibition) accelerated this process, establishing Axin2 as a therapeutic target in demyelinating disease.

    Evidence Axin2-KO mice and XAV939 treatment in hypoxic/demyelinating injury models

    PMID:21706018

    Open questions at the time
    • Whether Axin2 acts solely through Wnt suppression or additional pathways in OLPs was not resolved
    • Long-term remyelination efficacy was not assessed
  8. 2012 High

    The finding that APC/C-CDC20 degrades conductin at mitotic exit explained how Wnt/β-catenin activity peaks at G1/S, coupling destruction-complex activity to cell-cycle phase.

    Evidence Cell-cycle synchronization, CDC20 knockdown, CDC20-resistant conductin mutant overexpression, colony formation assays

    PMID:22322943

    Open questions at the time
    • The specific degron recognized by CDC20 in conductin was not mapped
    • Whether AXIN1 is similarly targeted by APC/C-CDC20 was not tested
  9. 2012 High

    Extension of the Snail1-stabilization mechanism to colorectal cancer demonstrated that AXIN2 promotes metastasis by driving EMT, revealing a pro-oncogenic facet of an otherwise tumor-suppressive gene.

    Evidence Axin2 siRNA in CRC cells; Snail1/EMT marker analysis; in vivo metastasis assays

    PMID:22745173

    Open questions at the time
    • Context-dependent switch between tumor-suppressive (β-catenin degradation) and pro-oncogenic (Snail1 stabilization) functions was not mechanistically explained
    • Patient stratification based on AXIN2 expression for prognosis was not addressed
  10. 2019 High

    Identification of an aggregation-inhibiting sequence (aggregon) in the RGS domain of conductin/AXIN2 explained why AXIN2 is intrinsically less active than AXIN1 and provided a druggable target: peptides masking the aggregon induced polymerization and enhanced β-catenin degradation.

    Evidence Domain-swapping, aggregon point mutations, in vitro polymerization and β-catenin degradation assays, CRC growth inhibition

    PMID:31534175

    Open questions at the time
    • Structural basis of aggregon-mediated polymerization inhibition at atomic resolution was not solved
    • In vivo pharmacokinetics and specificity of the aggregon-targeting peptide were not characterized
  11. 2022 High

    Gαi2 was identified as an endogenous activator of conductin condensation by targeting its RGS-domain aggregon, connecting G-protein signaling to Wnt pathway suppression and providing a pharmacological route (guanabenz) to enhance AXIN2 activity.

    Evidence Gαi2 co-expression/knockdown; condensate imaging; β-catenin degradation assays; CRC xenograft models; guanabenz treatment

    PMID:35115535

    Open questions at the time
    • Whether other Gα subunits similarly regulate AXIN2 polymerization was not tested
    • The stoichiometry and dynamics of Gαi2–AXIN2 interaction in native cells were not measured
  12. 2023 High

    ALKBH5-mediated m6A demethylation of AXIN2 mRNA was shown to destabilize the transcript via loss of IGF2BP1 binding, adding an epitranscriptomic layer of AXIN2 regulation with consequences for Wnt-driven immunosuppression in colorectal cancer.

    Evidence MeRIP-seq, RNA IP, siRNA knockdown, humanized mouse models, allografts, Alkbh5 knockin mice

    PMID:37169182

    Open questions at the time
    • Specific m6A sites on AXIN2 mRNA critical for IGF2BP1 binding were not individually mutated
    • Whether this regulatory axis operates in normal tissue homeostasis was not tested
  13. 2023 Medium

    Discovery of an AXIN2–ENO1 interaction in ASD neurons linked Wnt scaffold activity to glycolytic metabolism and synaptic function, suggesting AXIN2 participates in metabolic regulation beyond its canonical destruction-complex role.

    Evidence Co-IP in mouse and human ASD neurons; XAV939 treatment; glycolysis assays; behavioral rescue in Shank3−/− and VPA mice

    PMID:37078424

    Open questions at the time
    • Directness and stoichiometry of AXIN2–ENO1 binding were not validated by a second method
    • Whether the metabolic effect requires intact β-catenin degradation activity of AXIN2 was not tested
    • Replication in independent labs is needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of RGS-domain aggregon regulation, how AXIN2 switches between tumor-suppressive (β-catenin degradation) and pro-invasive (Snail1 stabilization) functions in different cellular contexts, and whether AXIN2's non-canonical roles at centrosomes and in metabolism are mechanistically linked.
  • No high-resolution structure of full-length AXIN2 or its condensates exists
  • Context-dependent switching between tumor suppression and EMT promotion is not mechanistically defined
  • Centrosomal, metabolic, and destruction-complex functions have not been integrated into a unified model

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1640170 Cell Cycle 1
Partners
APCCDC20CNAP1CTNNB1ENO1GNAI2GSK3BSNAI1
Complex memberships
β-catenin destruction complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 AXIN2 is a direct transcriptional target of the Wnt/β-catenin pathway, induced through TCF/LEF binding sites in its promoter and first intron; mutation or deletion of these sites abolished β-catenin-mediated induction, establishing a negative feedback loop where AXIN2 promotes β-catenin phosphorylation and degradation. Reporter constructs with promoter/intron fragments, EMSA with Tcf/LEF sites, transgenic embryo expression, endogenous mRNA/protein induction assays Molecular and cellular biology High 11809808 11809809
2002 AXIN2/conductin functions as a negative regulator of Wnt signaling by inducing β-catenin degradation through functional interaction with the tumor suppressor APC and the serine/threonine kinase GSK3β. Co-functional studies in tumor cell lines with dominant-negative TCF, Wnt-1 and Dishevelled activation, western blot for β-catenin Molecular and cellular biology High 11809809
2006 Canonical Wnt signaling stabilizes the Snail1 zinc-finger transcription factor through an Axin2-GSK3β axis: Axin2 acts as a nucleocytoplasmic chaperone for GSK3β, relocating it from the nucleus, thereby reducing GSK3β-mediated Snail1 phosphorylation and degradation to drive EMT and breast cancer invasion. Knockdown/overexpression in breast cancer cells, nuclear/cytoplasmic fractionation, Snail1 protein turnover assays, invasion assays Nature cell biology High 17072303
2005 Axin and Axin2 proteins are functionally equivalent in vivo; knockin of Axin2 cDNA under the Axin locus rescues Axin-null lethality, demonstrating that their different phenotypes arise from distinct expression patterns rather than different biochemical activities. Knockin mouse generation (Axin locus replaced with Axin or Axin2 cDNA), viability and fertility assessment of homozygotes Molecular and cellular biology High 15899843
2005 Axin2 is expressed at osteogenic fronts and periosteum of developing sutures; targeted disruption of Axin2 causes craniosynostosis through enhanced β-catenin signaling, promoting osteoprogenitor expansion and accelerated osteoblast differentiation. Axin2-null mouse analysis, in vivo/in vitro osteoblast proliferation and differentiation assays, β-catenin signaling readouts Development (Cambridge, England) High 15790973
2006 In osteoprogenitors, β-catenin acts as a transcriptional co-activator driving cyclin D1 expression to promote proliferation; upon differentiation, β-catenin switches to an adhesion role via adherens junctions. Haploid deficiency of β-catenin rescues Axin2-null craniosynostosis, confirming that Axin2 suppresses both proliferative and adhesive β-catenin functions. Genetic rescue (Axin2-null × β-catenin heterozygous mice), BMP signaling assays, adherens junction analysis Developmental biology High 17113065
2010 Conductin/Axin2 localizes at centrosomes by binding to the centriole-associated protein C-Nap1, and promotes phosphorylation of β-catenin (Ser33/37, Thr41) at centrosomes; loss of conductin causes premature centrosome separation dependent on β-catenin but independent of β-catenin-mediated transcription. Co-immunoprecipitation (conductin–C-Nap1), knockdown/knockout, centrosome imaging, phospho-β-catenin mutant rescue, transcription inhibitor controls EMBO reports High 20300119
2011 Axin2 is required for normal kinetics of oligodendrocyte progenitor differentiation and remyelination; tankyrase inhibitor XAV939 stabilizes Axin2 levels in OLPs and accelerates their differentiation after hypoxic/demyelinating injury. Axin2 KO mice, XAV939 pharmacological stabilization, remyelination assays in brain and spinal cord injury models Nature neuroscience High 21706018
2012 Conductin/Axin2 levels peak at G2/M and are degraded by the APC/C cofactor CDC20, allowing maximal Wnt/β-catenin target gene activity at G1/S; CDC20-resistant conductin inhibits Wnt signaling and colony formation of colorectal cancer cells. Cell cycle synchronization, CDC20 knockdown, CDC20-resistant conductin overexpression, colony formation assays, β-catenin phosphorylation analysis EMBO reports High 22322943
2012 In colorectal cancer cells with activated Wnt signaling, Axin2 promotes oncogenic behavior by stabilizing Snail1 activity and driving EMT; silencing Axin2 decreases Snail1, reverses EMT, and inhibits invasion and metastasis. Axin2 siRNA knockdown in CRC cells, Snail1 activity assays, EMT markers, in vivo metastasis models, transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America High 22745173
2013 p53 regulates nuclear GSK3β levels via miR-34-mediated suppression of Axin2; Axin2 acts as a cytoplasmic anchor retaining GSK3β outside the nucleus, and its suppression increases nuclear GSK3β abundance, leading to decreased Snail expression. miR-34a overexpression, Axin2 UTR-reporter assays, nuclear/cytoplasmic GSK3β fractionation, Snail protein level measurement, miR-sponge construct Cell cycle (Georgetown, Tex.) Medium 23624843
2014 Conductin/Axin2 shows reduced binding to Dvl2 compared to Axin1, making β-catenin degradation by conductin relatively insensitive to Dvl-mediated inhibition; this insensitivity to upstream Wnt pathway components is a key feature of conductin's role as a negative-feedback regulator. Domain-swap constructs, Co-IP of conductin/axin with Dvl2, β-catenin degradation assays with Dvl2 co-expression Journal of cell science Medium 25380820
2017 AXIN2 is the rate-limiting scaffold for formation of tankyrase-inhibitor-induced degradasomes (β-catenin destruction complex assemblies); depletion of AXIN2 (but not AXIN1) substantially impairs degradasome formation and β-catenin degradation in colorectal cancer cells. siRNA knockdown of AXIN1 vs AXIN2 in SW480 cells treated with tankyrase inhibitor G007-LK, immunofluorescence of degradasomes, β-catenin levels PloS one Medium 28107521
2019 Conductin/Axin2 contains an aggregation site (aggregon) in its RGS domain that prevents its polymerization and limits its activity; mutations masking this aggregon enhance conductin polymerization and β-catenin degradation. A peptide targeting this aggregon induces conductin polymerization, enhancing β-catenin degradation and suppressing colorectal cancer growth. Domain-swapping between axin and conductin, point mutations of aggregon, in vitro polymerization assays, β-catenin degradation assays, colorectal cancer cell growth assays Nature communications High 31534175
2022 Gαi2, a subunit of trimeric G-proteins, induces conductin/Axin2 condensation by targeting the polymerization-inhibiting aggregon in its RGS domain, promoting conductin-mediated β-catenin degradation and Wnt pathway suppression; the FDA-approved drug guanabenz activates Gαi2 to inhibit Wnt signaling via conductin condensation. Gαi2 co-expression/knockdown, condensate imaging, β-catenin degradation assays, colorectal cancer xenograft models, guanabenz treatment Nature communications High 35115535
2009 Axin2 regulates bone remodeling by controlling β-catenin-BMP2/4-Osx signaling in osteoblasts; Axin2 KO mice show increased trabecular bone mass and osteoblast differentiation, with elevated BMP2/4 expression and phospho-Smad1/5, and BMP2/4 deletion blocks β-catenin-induced osteoblast marker expression. Axin2-null mice, BMS cell isolation, β-catenin conditional deletion, BIO chemical inhibitor, Bmp2/4-flox adenoviral Cre deletion, siRNA knockdown of Osx Journal of cell science High 19737815
2013 Runx2 represses Axin2 transcription through binding to multiple Axin2 promoter regions in a manner dependent on Hdac3; haploinsufficiency of Runx2 in Axin2-null mice rescues craniosynostosis, placing Runx2-Hdac3 upstream of Axin2 in intramembranous bone development. ChIP (Runx2 at Axin2 promoter), Hdac3 co-repressor assay, Axin2-null × Runx2-heterozygous double mutant mouse rescue The Journal of biological chemistry High 23300083
2003 TCF-4 interacts with the transcriptional co-repressor CtBP1 via its C-terminus; CtBP1 represses TCF/β-catenin-dependent transcription including endogenous Axin2/conductin expression, and this repression is relieved by histone deacetylase inhibition (trichostatin A), indicating HDAC-dependent co-repressor activity. Co-IP of TCF-4 and CtBP1, synthetic promoter reporter assay, endogenous Axin2 mRNA measurement, trichostatin A treatment Nucleic acids research Medium 12711682
2011 In Axin2(canp) mutant mice carrying a V26D substitution in an N-terminal motif, Axin2 protein is more stable than wild type, leading to decreased Wnt signaling in most tissues but paradoxical increased Wnt activity in the late primitive streak; tankyrase inhibitor-induced Axin stabilization in wild-type embryos recapitulates this tissue-specific paradox. ENU-induced V26D knockin mice, Wnt reporter readouts in different tissues, tankyrase inhibitor treatment of wild-type embryos Proceedings of the National Academy of Sciences of the United States of America Medium 21555575
2017 Rap1b acts downstream of Axin2 in skeletal progenitor cells; Axin2 regulates Rap1b through modulation of canonical BMP signaling, and Rap1b-mediated inhibition of MAPK antagonizes FGF signaling to repress osteoblast differentiation while promoting chondrogenesis. Axin2 and Rap1b knockout mice, genetic epistasis, BMP/FGF/MAPK signaling assays, cell fate analysis Journal of bone and mineral research Medium 28520221
2023 Axin2 suppresses p53 signaling at the post-transcriptional level to maintain neural progenitor cell fitness; in genetic mosaic conditions, Axin2-deficient cells are eliminated by p53-dependent apoptosis (cell competition), and combined Axin2/p53 loss increases cortical area and thickness. Mosaic Axin2 knockout vs. homogeneous knockout mice, genetic double mutant (Axin2 + Trp53), cortical area/thickness measurement, apoptosis assays Developmental cell Medium 37054704
2023 ALKBH5, an m6A RNA eraser, binds and demethylates AXIN2 mRNA, causing its dissociation from the m6A reader IGF2BP1 and consequent degradation, thereby hyperactivating Wnt/β-catenin signaling and inducing DKK1-mediated immunosuppression in colorectal cancer. MeRIP-seq, RNA IP, siRNA knockdown, humanized mouse models, allografts, Alkbh5 knockin mice Gastroenterology High 37169182
2023 In ASD neurons, Axin2 interacts with the glycolytic enzyme ENO1; the tankyrase inhibitor XAV939 blocks Axin2/ENO1 interaction and stabilizes Axin2, shifting the glycolysis/oxidative phosphorylation balance and rescuing synaptic maturation and social behavior deficits. Co-IP of Axin2 and ENO1 in ASD mouse/human neurons, XAV939 treatment, glycolysis assays, behavioral rescue in Shank3-/- and VPA-treated mice EMBO molecular medicine Medium 37078424
2005 E2F1 upregulates Axin2 by two independent mechanisms: direct transcriptional activation of a specific 5' UTR variant via canonical E2F binding sites, and stabilization of Axin2 mRNA, establishing Axin2 as a point of cross-talk between the Rb/E2F and Wnt/β-catenin pathways. Reporter assays with E2F binding site mutations, mRNA stability assays, E2F1 overexpression Biochemical and biophysical research communications Medium 15766563
2016 Barx2 is recruited to TCF/LEF binding sites at the Axin2 gene, recruits β-catenin and the co-activator GRIP-1, and induces H3K-acetylation to activate Axin2 transcription; conversely, Pax7 represses Axin2 promoter activity via HDAC1-mediated histone deacetylation. ChIP for Barx2, β-catenin, GRIP-1, and HDAC1 at Axin2 locus; promoter/intron luciferase reporter assays; myoblast overexpression/knockdown Stem cells (Dayton, Ohio) Medium 27144473

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Molecular and cellular biology 1457 11809808
2002 Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Molecular and cellular biology 891 11809809
2015 Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver. Nature 540 26245375
2006 A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nature cell biology 538 17072303
2004 Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. American journal of human genetics 492 15042511
2002 Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 398 12101426
2001 Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors. Proceedings of the National Academy of Sciences of the United States of America 311 11752446
2011 Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination. Nature neuroscience 288 21706018
2005 The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development (Cambridge, England) 281 15790973
2019 CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/β-catenin signaling via transactivation of GSK-3β and Axin2 expression. Cell death & disease 154 30631044
2019 AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration. Cell stem cell 130 31866224
2023 ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy. Gastroenterology 125 37169182
2012 Canonical Wnt suppressor, Axin2, promotes colon carcinoma oncogenic activity. Proceedings of the National Academy of Sciences of the United States of America 125 22745173
2016 c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway. Cancer research 117 27197202
2011 Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. American journal of medical genetics. Part A 117 21626677
2014 AXIN1 and AXIN2 variants in gastrointestinal cancers. Cancer letters 115 25236910
2003 HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells. Nucleic acids research 108 12711682
2005 Mouse axin and axin2/conductin proteins are functionally equivalent in vivo. Molecular and cellular biology 106 15899843
2009 Axin2 controls bone remodeling through the beta-catenin-BMP signaling pathway in adult mice. Journal of cell science 98 19737815
2019 Endometrial Axin2+ Cells Drive Epithelial Homeostasis, Regeneration, and Cancer following Oncogenic Transformation. Cell stem cell 94 31883834
2013 p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells. Cell cycle (Georgetown, Tex.) 92 23624843
2006 Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation. Developmental biology 91 17113065
2006 Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability. Oncogene 86 16247484
2012 Cell cycle control of Wnt/β-catenin signalling by conductin/axin2 through CDC20. EMBO reports 82 22322943
2006 Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. Journal of human genetics 79 16432638
2013 Lineage tracing with Axin2 reveals distinct developmental and adult populations of Wnt/β-catenin-responsive neural stem cells. Proceedings of the National Academy of Sciences of the United States of America 78 23589866
2021 Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2. Oncogene 70 33824474
2011 AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome. American journal of medical genetics. Part A 69 21416598
2010 Conductin/axin2 and Wnt signalling regulates centrosome cohesion. EMBO reports 69 20300119
1999 Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics 63 10049590
2018 Esculetin suppresses tumor growth and metastasis by targeting Axin2/E-cadherin axis in colorectal cancer. Biochemical pharmacology 57 29534875
2008 Axis inhibition protein 2 (AXIN2) polymorphisms and tooth agenesis. Archives of oral biology 55 18790474
2016 Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease. Cardiovascular research 54 28069701
2015 Coordinated action of Axin1 and Axin2 suppresses β-catenin to regulate muscle stem cell function. Cellular signalling 51 25866367
2016 Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers. Development (Cambridge, England) 50 27578179
2014 Negative-feedback regulation of the Wnt pathway by conductin/axin2 involves insensitivity to upstream signalling. Journal of cell science 49 25380820
2011 Tissue-specific roles of Axin2 in the inhibition and activation of Wnt signaling in the mouse embryo. Proceedings of the National Academy of Sciences of the United States of America 49 21555575
2017 MicroRNA-221-3p promotes pulmonary artery smooth muscle cells proliferation by targeting AXIN2 during pulmonary arterial hypertension. Vascular pharmacology 47 28694128
2007 Mutations of the Wnt antagonist AXIN2 (Conductin) result in TCF-dependent transcription in medulloblastomas. International journal of cancer 47 17373666
2018 LncRNA miR143HG suppresses bladder cancer development through inactivating Wnt/β-catenin pathway by modulating miR-1275/AXIN2 axis. Journal of cellular physiology 46 30471109
2008 Frameshift mutations of Wnt pathway genes AXIN2 and TCF7L2 in gastric carcinomas with high microsatellite instability. Human pathology 45 18755497
2021 Zeb2/Axin2-Enriched BMSC-Derived Exosomes Promote Post-Stroke Functional Recovery by Enhancing Neurogenesis and Neural Plasticity. Journal of molecular neuroscience : MN 44 34401997
2019 miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2. Scientific reports 43 31273221
2013 Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis 43 23393221
2013 A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia. European journal of human genetics : EJHG 43 23838596
2008 Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in lung tumorigenesis. Oncogene 43 18372914
2019 An aggregon in conductin/axin2 regulates Wnt/β-catenin signaling and holds potential for cancer therapy. Nature communications 40 31534175
2015 miR-107 promotes hepatocellular carcinoma cell proliferation by targeting Axin2. International journal of clinical and experimental pathology 39 26191213
2010 Axin2 regulates chondrocyte maturation and axial skeletal development. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 38 19623616
2006 Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. International journal of molecular medicine 38 16820935
2022 Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth. Nature communications 37 35115535
2017 Differential Roles of AXIN1 and AXIN2 in Tankyrase Inhibitor-Induced Formation of Degradasomes and β-Catenin Degradation. PloS one 37 28107521
2006 Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype. Orthodontics & craniofacial research 36 16918677
2004 Mutations and elevated transcriptional activity of conductin (AXIN2) in hepatoblastomas. The Journal of pathology 36 15538750
2013 Novel missense mutations in the AXIN2 gene associated with non-syndromic oligodontia. Archives of oral biology 35 24581859
2013 Runx2 protein represses Axin2 expression in osteoblasts and is required for craniosynostosis in Axin2-deficient mice. The Journal of biological chemistry 34 23300083
2015 The roles of AXIN2 in tumorigenesis and epigenetic regulation. Familial cancer 33 25504512
2006 Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis. Human mutation 33 16941501
2011 Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Archives of oral biology 32 21530942
2006 Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the somitogenesis clock of mice. Developmental dynamics : an official publication of the American Association of Anatomists 31 17013874
2001 Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene. Cytogenetics and cell genetics 30 11474173
2021 Evaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines. Scientific reports 29 33811251
2017 Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis. Oncogene 29 28783177
2013 MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell. Molecular and cellular biochemistry 29 24166197
2009 Strong association between lung cancer and the AXIN2 polymorphism. Molecular medicine reports 29 21475939
2021 Curcumin suppresses colorectal tumorigenesis via the Wnt/β-catenin signaling pathway by downregulating Axin2. Oncology letters 28 33574925
2017 Snail and Axin2 expression predict the malignant transformation of oral leukoplakia. Oral oncology 28 28939076
2013 Absence of endochondral ossification and craniosynostosis in posterior frontal cranial sutures of Axin2(-/-) mice. PloS one 28 23936395
2017 Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer. Oncogenesis 27 28368388
2017 Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 27 28520221
2014 DNA methylation alterations of AXIN2 in serrated adenomas and colon carcinomas with microsatellite instability. BMC cancer 26 24964857
2014 The Axin2 rs2240308 polymorphism and susceptibility to lung cancer in a Chinese population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 25091576
2012 Association of AXIN2 with non-syndromic oral clefts in multiple populations. Journal of dental research 26 22370446
2020 GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis. International journal of molecular sciences 25 32575385
2018 Pygo2 Regulates Adiposity and Glucose Homeostasis via β-Catenin-Axin2-GSK3β Signaling Pathway. Diabetes 25 30279163
2016 Barx2 and Pax7 Regulate Axin2 Expression in Myoblasts by Interaction with β-Catenin and Chromatin Remodelling. Stem cells (Dayton, Ohio) 24 27144473
2014 Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer. Oncology letters 24 25013500
2019 Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene. Familial cancer 23 30671715
2016 Loss of Axin2 Causes Ocular Defects During Mouse Eye Development. Investigative ophthalmology & visual science 23 27701636
2022 Hederagenin ameliorates cisplatin-induced acute kidney injury via inhibiting long non-coding RNA A330074k22Rik/Axin2/β-catenin signalling pathway. International immunopharmacology 22 36155281
2018 MiR-183 maintains canonical Wnt signaling activity and regulates growth and apoptosis in bladder cancer via targeting AXIN2. European review for medical and pharmacological sciences 22 30070321
2023 Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2. Journal of cellular and molecular medicine 21 37488774
2022 The nonredundant nature of the Axin2 regulatory network in the canonical Wnt signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 21 35197279
2018 miR-3120-5p promotes colon cancer stem cell stemness and invasiveness through targeting Axin2. Biochemical and biophysical research communications 21 29307822
2015 A Novel AXIN2 Missense Mutation Is Associated with Non-Syndromic Oligodontia. PloS one 21 26406231
2017 Mutations in AXIN2 gene as a risk factor for tooth agenesis and cancer: A review. Neuro endocrinology letters 20 28759178
2016 Functional analysis of a novel missense mutation in AXIN2 associated with non-syndromic tooth agenesis. European journal of oral sciences 20 27090353
2015 MiR-374a promotes the proliferation of osteosarcoma cell proliferation by targeting Axin2. International journal of clinical and experimental pathology 19 26617789
2022 LncRNA GAS5 regulates the Wnt/β-catenin pathway through the miR-18a-5p/AXIN2/GSK3β axis to inhibit the proliferation and migration of bladder cancer cells. Carcinogenesis 18 36331809
2021 MicroRNA-1246 by Targeting AXIN2 and GSK-3β Overcomes Drug Resistance and Induces Apoptosis in Chemo-resistant Leukemia Cells. Journal of Cancer 18 34093820
2011 Identification of genetic alterations of AXIN2 gene in adrenocortical tumors. The Journal of clinical endocrinology and metabolism 18 21733995
2023 Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development. Developmental cell 17 37054704
2023 Axin2 coupled excessive Wnt-glycolysis signaling mediates social defect in autism spectrum disorders. EMBO molecular medicine 17 37078424
2015 MicroRNA-374a promotes esophageal cancer cell proliferation via Axin2 suppression. Oncology reports 17 26252180
2021 Rare germline variants in the AXIN2 gene in families with colonic polyposis and colorectal cancer. Familial cancer 16 34817745
2020 The Axin2-snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma. BMC cancer 16 33046030
2013 Mutational analysis of AXIN2, MSX1, and PAX9 in two Mexican oligodontia families. Genetics and molecular research : GMR 16 24222224
2005 E2F1 up-regulates the expression of the tumour suppressor axin2 both by activation of transcription and by mRNA stabilisation. Biochemical and biophysical research communications 16 15766563
2020 A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells. Genesis (New York, N.Y. : 2000) 15 32643876
2017 Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A multiple interaction analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 28378643