Affinage

AXIN2

Axin-2 · UniProt Q9Y2T1

Length
843 aa
Mass
93.6 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AXIN2 (conductin/Axil) is a scaffold protein that operates as the central node of a negative feedback loop in Wnt/β-catenin signaling: it is itself a direct transcriptional target of β-catenin-TCF/LEF, induced through TCF/LEF sites in its promoter and first intron, and the resulting protein joins the β-catenin destruction complex to drive β-catenin N-terminal phosphorylation (Ser33/37, Thr41) and degradation, thereby limiting Wnt signal duration (PMID:11809808, PMID:11940574, PMID:20300119). AXIN2 and AXIN1 are functionally interchangeable proteins whose distinct biology derives from differing expression rather than intrinsic function (PMID:15899843), yet AXIN2 has non-redundant, context-specific roles — it is selectively required for degradasome formation upon tankyrase inhibition (PMID:28107521) and cooperates with AXIN1 to restrain β-catenin in stem cell pools (PMID:25866367); its inhibitory activity depends on the C-terminal DIX domain (PMID:17373666). AXIN2 activity is tightly tuned at multiple post-transcriptional levels: a polymerization-inhibiting aggregon in its RGS domain limits its assembly and β-catenin-degrading capacity, a constraint relieved by Gαi2-induced condensation (PMID:31534175, PMID:35115535); its protein level oscillates across the cell cycle through APC/C-CDC20-mediated degradation at the G2/M-to-G1 transition (PMID:22322943); and its stability and mRNA abundance are controlled by tankyrase, alternative 5'UTRs, and TGF-β-driven mRNA decay and m6A-dependent turnover (PMID:21555575, PMID:15611123, PMID:29409120, PMID:37169182). Through this circuitry AXIN2 governs skeletal development and bone remodeling — its loss causes craniosynostosis and increased bone mass via β-catenin-BMP2/4-Osterix signaling and a Rap1b-integrated BMP/FGF axis — and is itself transcriptionally controlled by Runx2 and CDX2 (PMID:15790973, PMID:19737815, PMID:28520221, PMID:23300083, PMID:30631044). Beyond canonical Wnt regulation, AXIN2 localizes to centrosomes via C-Nap1 to maintain centrosome cohesion (PMID:20300119), suppresses p53 signaling post-transcriptionally to sustain neural progenitor fitness during cell competition (PMID:37054704), and interacts with the glycolytic enzyme ENO1 to modulate glycolysis/oxidative phosphorylation balance (PMID:37078424). In cancer it shows context-dependent roles, acting as a tumor suppressor whose enforced polymerization restrains colorectal cancer growth (PMID:31534175, PMID:35115535) yet, in other contexts, promoting EMT and metastasis by upregulating Snail1 (PMID:22745173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Established that AXIN2 is a direct β-catenin-TCF transcriptional target, defining the negative feedback architecture that distinguishes it from AXIN1.

    Evidence Reporter constructs, TCF/LEF site mutagenesis, EMSA, transgenic embryos, and inducible β-catenin/Wnt1/dnTCF-4 perturbation

    PMID:11809808 PMID:11940574

    Open questions at the time
    • Does not address how AXIN2 protein engages the destruction complex
    • Does not resolve tissue-specific differences in feedback strength
  2. 2005 High

    Showed AXIN2 and AXIN1 proteins are functionally equivalent in vivo, attributing their non-redundancy to expression patterns rather than protein function.

    Evidence Knockin mice expressing Axin2 cDNA from the Axin1 locus, scored for viability and fertility

    PMID:15899843

    Open questions at the time
    • Whole-organism rescue does not exclude cell-type-specific functional differences later observed in stem cells and degradasomes
  3. 2005 High

    Linked AXIN2 to skeletal development, showing its loss causes craniosynostosis via enhanced β-catenin-driven osteoprogenitor expansion.

    Evidence Axin2 knockout mice with osteoblast differentiation and β-catenin signaling readouts

    PMID:15790973

    Open questions at the time
    • Does not define upstream transcriptional control of Axin2 in sutures
    • Downstream osteogenic effectors not yet mapped
  4. 2009 High

    Extended AXIN2's skeletal role to adult bone remodeling and identified the β-catenin-BMP2/4-Osterix axis as the effector pathway.

    Evidence Axin2 KO mice, BMS cell differentiation, β-catenin deletion rescue, BMP2/4 conditional deletion, GSK3β inhibitor treatment

    PMID:19737815

    Open questions at the time
    • Does not establish whether BMP2/4 induction is direct or secondary to β-catenin
  5. 2010 High

    Identified a non-canonical centrosomal role: AXIN2 binds C-Nap1 and locally phosphorylates β-catenin to maintain centrosome cohesion.

    Evidence Conductin KO/KD, β-catenin KD, centrosome imaging, phospho-mutant β-catenin analysis, Wnt/GSK3 inhibitor treatment

    PMID:20300119

    Open questions at the time
    • Does not define how Wnt signaling temporally couples to centrosome splitting
    • Structural basis of C-Nap1 binding unknown
  6. 2012 High

    Revealed cell-cycle control of AXIN2 abundance via APC/C-CDC20 degradation at G2/M, coupling Wnt signaling output to the cell cycle.

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

    PMID:22322943

    Open questions at the time
    • Degron sequence recognized by CDC20 not fully mapped
    • Physiological consequence of cell-cycle Wnt oscillation in vivo unclear
  7. 2012 High

    Demonstrated a context-dependent oncogenic role in which AXIN2 drives EMT and metastasis through Snail1 upregulation, contrary to its canonical tumor-suppressor activity.

    Evidence AXIN2 silencing in CRC cells, Snail1 and EMT marker assays, in vitro/in vivo invasion and metastasis assays

    PMID:22745173

    Open questions at the time
    • Molecular basis for the switch between suppressive and oncogenic roles not defined
    • Whether Snail1 regulation is β-catenin-dependent unresolved
  8. 2007 Medium

    Mapped the DIX domain as required for AXIN2's Wnt-inhibitory function, since DIX deletion converts AXIN2 into a pathway activator.

    Evidence Wild-type vs DIX-deleted AXIN2 overexpression with luciferase Wnt reporters in medulloblastoma cells

    PMID:17373666

    Open questions at the time
    • Single-domain deletion; does not reconcile DIX with the later-described RGS aggregon control of polymerization
  9. 2007 Medium

    Positioned AXIN2 as a mediator of TGF-β/Wnt cross-talk in chondrocytes through Smad3-dependent suppression of Axin expression.

    Evidence Axin2-/- and Smad3-/- chondrocytes, TGF-β treatment, Smad3 reporters, Axin/β-catenin overexpression

    PMID:18083923

    Open questions at the time
    • Mechanism of Smad3-dependent Axin2 repression not detailed
    • Single lab
  10. 2011 Medium

    Established AXIN2 protein stability as a key tunable regulatory parameter, with tankyrase-dependent stabilization controlling tissue-specific Wnt output.

    Evidence ENU Axin2(canp) V26D stable allele, protein stability and tissue Wnt reporters, tankyrase inhibitor treatment of embryos; and OLP loss-of-function with XAV939 remyelination rescue

    PMID:21555575 PMID:21706018

    Open questions at the time
    • Mechanistic basis for paradoxical tissue-specific Wnt activation unresolved
    • Link between stability motif and tankyrase pathway not fully defined
  11. 2013 High

    Defined transcriptional control of AXIN2 by Runx2-Hdac3 repression and CDX2 activation, embedding it in bone and intestinal regulatory circuits.

    Evidence ChIP for Runx2 and CDX2 binding, Hdac3-dependent repression assays, Axin2-/-:Runx2+/- rescue, intestinal enhancer reporters

    PMID:23300083 PMID:23393221

    Open questions at the time
    • Interplay between repressive (Runx2) and activating (CDX2, β-catenin) inputs at the locus not integrated
  12. 2015 Medium

    Showed AXIN1 and AXIN2 are non-equivalent in satellite cells, cooperating to suppress β-catenin and maintain myoblast proliferation.

    Evidence siRNA knockdown of Axin1/Axin2 in WT and Axin2-null satellite cells, β-catenin localization/reporter, β-catenin rescue, proliferation/differentiation assays

    PMID:25866367

    Open questions at the time
    • Apparent conflict with whole-animal functional equivalence not mechanistically reconciled
    • Single lab
  13. 2017 Medium

    Distinguished AXIN2 from AXIN1 by its selective requirement for degradasome formation, and defined a Rap1b-dependent BMP/FGF integration node in skeletal stem cells.

    Evidence siRNA depletion in SW480 cells with tankyrase inhibitor and degradasome imaging; Rap1b-null mice and Axin2+ stem cell BMP/FGF analysis

    PMID:28107521 PMID:28520221

    Open questions at the time
    • Structural determinant of AXIN2-specific degradasome nucleation unknown
    • Direct biochemical link between Axin2 and Rap1b not shown
  14. 2019 High

    Identified the RGS-domain aggregon as a polymerization brake whose neutralization enhances β-catenin degradation, opening a therapeutic strategy in colorectal cancer.

    Evidence Axin1/Axin2 domain swapping, aggregon point mutagenesis, polymerization and β-catenin degradation assays, peptide treatment, CRC growth assays

    PMID:31534175

    Open questions at the time
    • Physiological trigger of aggregon relief not yet identified in this study
    • In vivo relevance of polymerization not established here
  15. 2019 High

    Demonstrated post-transcriptional silencing of AXIN2 by TGF-β-driven mRNA decay and m6A demethylation, linking AXIN2 loss to Wnt hyperactivation and immunosuppression.

    Evidence mRNA decay assays with tristetraprolin1 depletion and TβRIIΔk-fib mice; meRIP-seq with ALKBH5 knockin mice and IGF2BP1 reader analysis in CRC

    PMID:29409120 PMID:37169182

    Open questions at the time
    • How multiple RNA-level controls are prioritized in a given cell type unresolved
    • Interaction between mRNA decay and translational 5'UTR control not integrated
  16. 2022 High

    Identified Gαi2 as a partner that induces AXIN2 condensation by targeting the RGS aggregon, providing a druggable route to suppress Wnt signaling.

    Evidence Gαi2 overexpression/knockdown, condensation and β-catenin degradation assays, Wnt reporters, guanabenz treatment, CRC mouse models

    PMID:35115535

    Open questions at the time
    • Structural basis of Gαi2-aggregon engagement not resolved
    • Upstream signals controlling Gαi2 availability not defined
  17. 2023 High

    Expanded AXIN2's roles beyond Wnt by linking it to p53-dependent cell competition in neural progenitors and to ENO1-mediated metabolic control in neurons.

    Evidence Mosaic vs homogeneous Axin2 KO with Trp53 double KO and cortical phenotyping; Axin2/ENO1 co-interaction, XAV939 disruption, glycolysis and behavioral rescue in ASD models

    PMID:37054704 PMID:37078424

    Open questions at the time
    • Mechanism by which Axin2 post-transcriptionally suppresses p53 unknown
    • Whether ENO1 binding is Wnt-dependent unclear
    • Direct biochemical AXIN2-ENO1 interface not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AXIN2's many regulatory layers — transcriptional, translational, mRNA-decay, m6A, cell-cycle degradation, and aggregon-controlled polymerization — are integrated in vivo to select between its Wnt-scaffold, centrosomal, metabolic, and p53-suppressive functions remains unresolved.
  • No unified model reconciling pro- and anti-tumorigenic roles
  • Determinants of functional partner choice (destruction complex vs C-Nap1 vs ENO1) unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2
Partners
APCC-NAP1 (CEP250)CDC20CTNNB1ENO1GNAI2GSK3B
Complex memberships
β-catenin destruction complex / degradasome

Evidence

Reading pass · 26 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, activated through TCF/LEF binding sites in its promoter and first intron. Mutation or deletion of TCF/LEF sites greatly diminished induction by β-catenin, and mutation of site T2 abolished protein binding in an EMSA. This establishes Axin2 as part of a negative feedback loop that limits Wnt signal duration/intensity. Reporter constructs with 5.6-kb genomic fragment, TCF/LEF site mutagenesis, EMSA, transgenic embryo analysis, endogenous mRNA/protein induction assays Molecular and cellular biology High 11809808 11940574
2002 AXIN2 expression is strongly induced by activated β-catenin-TCF signaling via TCF binding sites in the AXIN2 promoter; dominant-negative TCF-4 represses AXIN2 expression. Restoration of wild-type APC suppresses AXIN2. This positions AXIN2 in a negative feedback pathway regulating Wnt signaling, distinct from AXIN1 which is not regulated by β-catenin-TCF. β-catenin-estrogen receptor fusion activation, Wnt1 overexpression, dominant-negative TCF-4, APC restoration, TCF binding site reporter assays The Journal of biological chemistry High 11940574
2005 Axin2 and Axin1 proteins are functionally equivalent in vivo. Knockin mice expressing Axin2 cDNA under the Axin1 locus (Axin^Ax2/Ax2) are apparently normal and fertile, demonstrating that the lack of redundancy between the two proteins in wild-type animals is due to their different expression patterns rather than different protein functions. Knockin mouse generation (Axin cDNA replaced with Axin2 cDNA), viability and fertility assessment of homozygous knockin mice Molecular and cellular biology High 15899843
2005 Axin2 is expressed at osteogenic fronts and periosteum of developing sutures; targeted disruption of Axin2 in mice causes craniosynostosis through enhanced β-catenin signaling, increased osteoprogenitor expansion, accelerated ossification, and stimulated osteoblast proliferation and differentiation. The craniofacial anomalies are mediated through activation of β-catenin signaling. Axin2 knockout mice, in vivo/in vitro osteoblast differentiation assays, β-catenin signaling analysis, osteogenic marker expression Development (Cambridge, England) High 15790973
2010 Conductin/Axin2 localizes at centrosomes by binding to the centriole-associated component C-Nap1. Knockout or knockdown of conductin leads to premature centrosome separation (splitting), which is abolished by knockdown of β-catenin. Conductin promotes phosphorylation of N-terminal serine/threonine residues (Ser33/37, Thr41) of centrosome-associated β-catenin; β-catenin mutated at these residues causes centrosomal splitting. Treatment with Wnts and GSK3 inhibition block β-catenin phosphorylation and induce centrosomal splitting. Conductin KO/KD, β-catenin KD, centrosome localization imaging, phospho-β-catenin mutant analysis, Wnt/GSK3 inhibitor treatment EMBO reports High 20300119
2011 Axin2 function is essential for normal kinetics of oligodendrocyte progenitor cell (OLP) differentiation and remyelination after injury. The small molecule tankyrase inhibitor XAV939 stabilizes Axin2 levels in OLPs and accelerates their differentiation and myelination after hypoxic and demyelinating injury. Axin2 loss-of-function in vivo, XAV939 (tankyrase inhibitor) treatment of OLPs from brain and spinal cord, remyelination assays after hypoxic/demyelinating injury Nature neuroscience High 21706018
2012 Conductin/Axin2 levels peak at G2/M and are rapidly degraded during return to G1. Conductin is degraded by the APC/C cofactor CDC20. CDC20 knockdown blocks Wnt signaling through conductin. CDC20-resistant conductin inhibits Wnt signaling and attenuates colony formation. β-catenin phosphorylation oscillates during the cell cycle in a conductin-dependent manner. Cell cycle synchronization, CDC20 knockdown, CDC20-resistant conductin mutant expression, Wnt signaling reporters, colony formation assays EMBO reports High 22322943
2012 Axin2 promotes colon carcinoma oncogenic activity (rather than acting as a tumor suppressor) by upregulating the transcriptional repressor Snail1, inducing epithelial-mesenchymal transition (EMT) and driving metastatic activity. Silencing Axin2 decreases Snail1 activity, reverses EMT, and inhibits CRC invasive and metastatic activities. Axin2 silencing in CRC cells, Snail1 activity assays, EMT marker analysis, invasion and metastasis assays in vitro and in vivo, Wnt-regulated transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America High 22745173
2009 Axin2 is a key negative regulator of bone remodeling in adult mice; its loss increases trabecular bone mass and bone formation rates, and increases nuclear β-catenin in BMS cells. Axin2 KO-enhanced osteoblast differentiation is reversed by β-catenin deletion. Axin2 regulates osteoblast differentiation through the β-catenin-BMP2/4-Osterix signaling pathway. Axin2 KO mice, bone marrow stromal cell isolation, in vitro β-catenin deletion rescue, BMP2/4 mRNA and pSmad1/5 analysis, GSK3β inhibitor BIO treatment, Bmp2/4 conditional deletion Journal of cell science High 19737815
2011 The Axin2(canp) V26D substitution in an N-terminal sequence motif results in a more stable Axin2 protein. Increased stability of Axin2 generally decreases Wnt signaling in most tissues but paradoxically enhances canonical Wnt activity in the late primitive streak. Treatment of wild-type embryos with a tankyrase inhibitor that stabilizes Axin proteins phenocopies this, confirming that Axin2 stability is a key regulatory mechanism. ENU-induced Axin2(canp) allele characterization, protein stability assays, tissue-specific Wnt signaling reporter analysis, tankyrase inhibitor treatment of embryos Proceedings of the National Academy of Sciences of the United States of America Medium 21555575
2017 Axin2 functions upstream of Rap1b in skeletal development: Axin2 regulates Rap1b through modulation of canonical BMP signaling. Rap1b acts as a signaling integrator for FGF and BMP downstream of Axin2; BMP-mediated activation of Rap1b promotes chondrogenic fate and inhibits MAPK/FGF-driven osteoblast differentiation. Genetic analysis of Rap1b-null mice, Axin2+ stem cell characterization, BMP/FGF signaling pathway analysis, osteogenic/chondrogenic differentiation assays Journal of bone and mineral research Medium 28520221
2013 Runx2 represses Axin2 transcription via Hdac3, by binding to multiple regions of the Axin2 promoter. Runx2 haploinsufficiency in Axin2-null mice rescues the craniosynostosis phenotype, placing Runx2 upstream of Axin2 in a pathway regulating intramembranous bone development. ChIP (Runx2 binding to Axin2 promoter), Hdac3-dependent repression assays, Axin2(-/-):Runx2(+/-) double mutant mice, skull morphology analysis The Journal of biological chemistry High 23300083
2015 In satellite cells (muscle stem cells), Axin1 and Axin2 have non-equivalent functions: Axin1 knockdown in Axin2-null cells strongly inhibits proliferation, induces differentiation, causes nuclear β-catenin localization, and activates TCF reporter activity. These effects are rescued by concomitant β-catenin knockdown, demonstrating that Axin1 and Axin2 cooperate to suppress β-catenin signaling and maintain myoblast proliferation. siRNA knockdown of Axin1 and Axin2 in WT and Axin2-null satellite cells, β-catenin localization/reporter assays, retroviral Axin2 overexpression, proliferation/differentiation assays Cellular signalling Medium 25866367
2004 Axin2 mRNA contains alternative 5'-untranslated regions (5'UTRs) that differentially regulate translational efficiency via short upstream reading frames and structural motifs. Proportional expression of each 5'UTR variant influences total Axin2 protein levels, establishing a translational control mechanism for Axin2 expression. 5'UTR reporter constructs, mRNA stability assays, translational efficiency measurements, characterization of upstream ORFs and secondary structures The Journal of biological chemistry Medium 15611123
2019 An aggregation site (aggregon) in the RGS domain of conductin/Axin2 prevents its polymerization and limits its activity relative to Axin1. Point mutations that neutralize this aggregon enhance conductin polymerization and β-catenin degradation. A short peptide that masks the aggregon induces conductin polymerization, enhances β-catenin degradation, inhibits β-catenin-dependent transcription, and represses colorectal cancer cell growth. Domain swapping between Axin1 and Axin2, point mutagenesis of aggregon, polymerization assays, β-catenin degradation assays, Wnt reporter assays, colorectal cancer cell growth assays, peptide treatment Nature communications High 31534175
2022 Gαi2 induces conductin/Axin2 condensation by targeting the polymerization-inhibiting aggregon in its RGS domain, thereby promoting conductin-mediated β-catenin degradation and inhibiting Wnt signaling. Transient Gαi2 expression inhibits Wnt signaling, Gαi2 knockdown activates it, and the Gαi2-activating drug guanabenz inhibits Wnt signaling via conductin, reducing colorectal cancer growth in vitro and in mouse models. Gαi2 overexpression/knockdown, conductin condensation assays, β-catenin degradation assays, Wnt reporter assays, guanabenz drug treatment, colorectal cancer mouse models Nature communications High 35115535
2017 AXIN2 is required for degradasome formation and β-catenin degradation upon tankyrase inhibition in SW480 cells. AXIN1 is not required for degradasome formation, whereas depletion of AXIN2 considerably impairs both degradasome formation and their capacity to degrade β-catenin. This reveals a differential and non-redundant role for AXIN2 (vs AXIN1) in the β-catenin destruction complex. siRNA depletion of AXIN1 and AXIN2 in SW480 cells, tankyrase inhibitor G007-LK treatment, degradasome imaging, β-catenin degradation assays PloS one Medium 28107521
2007 TGF-β suppresses the expression of both Axin1 and Axin2 in chondrocytes through a Smad3-dependent mechanism. In Axin2(-/-) chondrocytes, TGF-β treatment results in a sustained increase in β-catenin levels compared to wild-type. Overexpression of Axin2 enhances TGF-β signaling while overexpression of β-catenin inhibits Smad3-sensitive reporters, demonstrating that Axin2 mediates cross-talk between TGF-β and Wnt/β-catenin signaling pathways. Axin2(-/-) and Smad3(-/-) chondrocytes, TGF-β treatment, Smad3-sensitive reporter assays, β-catenin measurement, Axin overexpression Annals of the New York Academy of Sciences Medium 18083923
2008 Epigenetic silencing of AXIN2 through TGF-β-dependent increase in AXIN2 mRNA decay reduces Axin2 protein levels in systemic sclerosis fibroblasts, causing sensitization to canonical Wnt ligands. XAV939-mediated stabilization of Axin2 (via tankyrase inhibition) reverses the increased Wnt response, demonstrating that reduced Axin2 bioavailability is the mechanistic basis for TGF-β-primed Wnt activation. TGF-β treatment of fibroblasts, Axin2 mRNA decay assays, TGFβRI blockade, siRNA-mediated tristetraprolin1 depletion, XAV939 treatment, TOPflash reporter assays, Axin2 gain/loss-of-function Arthritis & rheumatology Medium 29409120
2023 Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain neural progenitor cell (NPC) fitness. In a mosaic setting, Axin2-deficient NPCs behave as 'losers' and undergo p53-dependent apoptotic elimination via cell competition. Homogeneous Axin2 ablation does not promote cell death. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness. Mosaic genetic mosaicism induction, Axin2-conditional KO, p53/Trp53 conditional KO, double conditional KO, NPC apoptosis quantification, cortical size measurement Developmental cell High 37054704
2023 Axin2 interacts with the glycolytic enzyme enolase 1 (ENO1) in ASD neurons. An Axin2 stabilizer (XAV939) blocked the Axin2/ENO1 interaction, switched glycolysis/oxidative phosphorylation balance, promoted synaptic maturation, and rescued social function in ASD mouse models. Co-interaction assays for Axin2/ENO1, XAV939 treatment, glycolysis measurement, synaptic maturation assays, behavioral testing in Shank3(-/-) and VPA-treated mice EMBO molecular medicine Medium 37078424
2007 Overexpression of wild-type AXIN2 inhibits Wnt-3a-stimulated TCF/LEF-dependent transcription in medulloblastoma cells. In contrast, an AXIN2 mutant with a deleted C-terminal DIX domain activates the Wnt signaling pathway, demonstrating that the DIX domain is required for Axin2's inhibitory function on Wnt signaling. Wild-type and DIX-domain-deleted AXIN2 overexpression in MB cell lines, luciferase Wnt reporter assays, Wnt-3a stimulation International journal of cancer Medium 17373666
2019 ALKBH5, an RNA N6-methyladenosine (m6A) eraser, binds and demethylates AXIN2 mRNA, causing its dissociation from the m6A reader IGF2BP1 and subsequent degradation. Loss of AXIN2 mRNA stability results in hyperactivated Wnt/β-catenin signaling, increased DKK1, and MDSC-driven immunosuppression in colorectal cancer. Methylated RNA immunoprecipitation sequencing, RNA sequencing, ALKBH5 knockin mice, allografts, CD34+ humanized mice, flow cytometry, in vitro/in vivo functional assays Gastroenterology High 37169182
2019 CDX2 transcriptionally activates AXIN2 expression by directly binding to an upstream enhancer of AXIN2, as confirmed by dual-luciferase reporter and quantitative ChIP assays. CDX2 knockdown reduces AXIN2 expression and enhances Wnt/β-catenin signaling, while CDX2 overexpression increases AXIN2 and suppresses Wnt signaling. Dual-luciferase reporter assay, quantitative ChIP, CDX2 knockdown/overexpression, Wnt pathway activity assays (TOP/FOP-Flash), β-catenin target gene expression Cell death & disease Medium 30631044
2013 CDX2 activates AXIN2 promoter activity via intestinal cell-specific enhancer elements, as shown by transfection of intestinal and non-intestinal cell lines. Suppressed CDX2 is associated with endogenous downregulation of AXIN2 expression in Caco-2 cells, confirming CDX2 as a transcriptional activator of AXIN2. Promoter-enhancer reporter transfection assays, CDX2 knockdown, endogenous AXIN2 mRNA quantification Carcinogenesis Medium 23393221
2018 TGF-β activation decreases Axin2 expression in fibroblasts through a TGF-β-dependent increase in Axin2 mRNA decay, mediated by tristetraprolin 1. This reduction in Axin2 bioavailability is necessary for TGF-β to prime canonical Wnt signaling. In vivo validation in TβRIIΔk-fib transgenic mice confirms decreased Axin2 mRNA and protein in fibroblasts with dysregulated TGF-β signaling. mRNA decay assays, siRNA knockdown of tristetraprolin 1, TGFβRI blockade, Axin2 gain/loss-of-function, TOPflash assay, TβRIIΔk-fib transgenic mouse analysis Arthritis & rheumatology Medium 29409120

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 1466 11809808
2004 Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. American journal of human genetics 493 15042511
2002 Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 398 12101426
2002 Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling. The Journal of biological chemistry 319 11940574
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 289 21706018
2005 The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development (Cambridge, England) 285 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 158 30631044
2019 AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration. Cell stem cell 134 31866224
2023 ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy. Gastroenterology 127 37169182
2012 Canonical Wnt suppressor, Axin2, promotes colon carcinoma oncogenic activity. Proceedings of the National Academy of Sciences of the United States of America 126 22745173
2016 c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway. Cancer research 118 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 116 25236910
2005 Mouse axin and axin2/conductin proteins are functionally equivalent in vivo. Molecular and cellular biology 106 15899843
2016 Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling. Proceedings of the National Academy of Sciences of the United States of America 104 26903625
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 96 31883834
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 83 22322943
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 80 23589866
2006 Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. Journal of human genetics 80 16432638
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 71 33824474
2011 AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome. American journal of medical genetics. Part A 71 21416598
2011 Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and Axin2(LacZ) during murine lung development and repair. PloS one 71 21858009
2010 Conductin/axin2 and Wnt signalling regulates centrosome cohesion. EMBO reports 69 20300119
2007 Axin1 and Axin2 are regulated by TGF- and mediate cross-talk between TGF- and Wnt signaling pathways. Annals of the New York Academy of Sciences 66 18083923
1999 Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics 63 10049590
2019 miR-221-3p and miR-15b-5p promote cell proliferation and invasion by targeting Axin2 in liver cancer. Oncology letters 60 31814849
2019 Axin2+-Mesenchymal PDL Cells, Instead of K14+ Epithelial Cells, Play a Key Role in Rapid Cementum Growth. Journal of dental research 57 31454276
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
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 48 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 41 31534175
2022 Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth. Nature communications 39 35115535
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 39 19623616
2020 TFRC promotes epithelial ovarian cancer cell proliferation and metastasis via up-regulation of AXIN2 expression. American journal of cancer research 38 32064157
2017 Differential Roles of AXIN1 and AXIN2 in Tankyrase Inhibitor-Induced Formation of Degradasomes and β-Catenin Degradation. PloS one 37 28107521
2004 Mutations and elevated transcriptional activity of conductin (AXIN2) in hepatoblastomas. The Journal of pathology 36 15538750
2016 Axin2-expressing cells execute regeneration after skeletal injury. Scientific reports 35 27853243
2013 Novel missense mutations in the AXIN2 gene associated with non-syndromic oligodontia. Archives of oral biology 35 24581859
2018 Transforming Growth Factor β Activation Primes Canonical Wnt Signaling Through Down-Regulation of Axin-2. Arthritis & rheumatology (Hoboken, N.J.) 34 29409120
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
2022 Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force. Journal of dental research 32 35001706
2011 Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Archives of oral biology 32 21530942
2021 Curcumin suppresses colorectal tumorigenesis via the Wnt/β-catenin signaling pathway by downregulating Axin2. Oncology letters 30 33574925
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
2016 SOX7 co-regulates Wnt/β-catenin signaling with Axin-2: both expressed at low levels in breast cancer. Scientific reports 29 27188720
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 28 28520221
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
2006 Regulation of axin2 expression at the levels of transcription, translation and protein stability in lung and colon cancer. Cancer letters 27 15885887
2021 circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/β-catenin signal pathway. BMC genomics 26 34706645
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
2016 Loss of Axin2 Causes Ocular Defects During Mouse Eye Development. Investigative ophthalmology & visual science 24 27701636
2004 Expression of axin2 is regulated by the alternative 5'-untranslated regions of its mRNA. The Journal of biological chemistry 24 15611123
2022 Hederagenin ameliorates cisplatin-induced acute kidney injury via inhibiting long non-coding RNA A330074k22Rik/Axin2/β-catenin signalling pathway. International immunopharmacology 23 36155281
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
2012 Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a Polish population. Birth defects research. Part A, Clinical and molecular teratology 23 22887353
2021 Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma. Gastroenterology 22 33465373
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
2010 AXIN2 polymorphism and its association with prostate cancer in a Turkish population. Medical oncology (Northwood, London, England) 20 21069480
2021 MicroRNA-1246 by Targeting AXIN2 and GSK-3β Overcomes Drug Resistance and Induces Apoptosis in Chemo-resistant Leukemia Cells. Journal of Cancer 19 34093820
2015 MiR-374a promotes the proliferation of osteosarcoma cell proliferation by targeting Axin2. International journal of clinical and experimental pathology 19 26617789
2023 Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development. Developmental cell 18 37054704
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
2011 Identification of genetic alterations of AXIN2 gene in adrenocortical tumors. The Journal of clinical endocrinology and metabolism 18 21733995
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
2008 Axin2 expression identifies progenitor cells in the murine prostate. The Prostate 17 18563716
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

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