Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (643 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A complex signaling pathway whose name is derived from the drosophila Wg gene, and the vertebrate INT gene. The signaling pathway is initiated by the binding of wnt proteins to cell surface wnt receptors which interact with the axin signaling complex and an array of second messengers that influence the actions of beta catenin.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Pathway, Wnt Signaling; Signaling Pathway, Wnt; Wnt Signaling Pathways; Wnt Pathway; Pathway, Wnt; Wnt beta-Catenin Signaling Pathway; Wnt beta Catenin Signaling Pathway; Wnt Pathway, Canonical.
Where it fits in the MeSH classification
- Broader topics
- Signal Transduction
Related concepts
- Drosophila
- Wnt Proteins
- Wnt Receptors
- Axin Signaling Complex
- Beta Catenin
Research landscape
PubMed indexes 19,450 records tagged with the MeSH heading “Wnt Signaling Pathway” (counts retrieved 2026-10-29). 9,339 of them (48.0%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 10,335 records.
Reviews account for 2,146 records (11.0%) and meta-analyses for 24. Randomized controlled trials number 27 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 2 |
| 2010-2019 | 10,335 |
| 2020 onward | 9,339 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,146 | 11.0% |
| Meta-analyses | 24 | 0.1% |
| Randomized controlled trials | 27 | 0.1% |
Method: PubMed query "Wnt Signaling Pathway"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis | 2025 | Research article Design not recorded in structured metadata | 12 | cc by PMID 40604818 · DOI · PMC12220525 |
| Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling | 2026 | Research article Design not recorded in structured metadata | 10 | cc by PMID 41629672 · DOI · PMC12900645 |
| Preventive Effect of Fisetin on Follicular Granulosa Cells Senescence via Attenuating Oxidative Stress and Upregulating the Wnt/β-Catenin Signaling Pathway | 2025 | Research article Design not recorded in structured metadata | 9 | cc by PMID 41227350 · DOI · PMC12610666 |
STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundSerine/threonine kinase 3 (STK3) is recognized as a key regulator in Hippo pathway and a tumor-suppressing gene in various cancer types.
- Closing excerpt
- Moreover, STK3-targeted therapy offered a novel approach to concur acquired chemo-resistance in GC patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (264 words)
BackgroundSerine/threonine kinase 3 (STK3) is recognized as a key regulator in Hippo pathway and a tumor-suppressing gene in various cancer types. However, its non-canonical role has been gradually revealed in cancer development.MethodsOur objective is to elucidate the upregulation pattern and molecular mechanisms of STK3 in advancing gastric cancer (GC) progression. The regulation of YAP1 on STK3 was assessed through a combination of bulk and single-cell RNA-sequencing, Western blot, ChIP-qPCR, gene knockout mouse models, and functional rescue assays. The oncogenic roles of STK3 were confirmed through subcutaneous xenograft formation models and functional assays including spheroid formation and organoid growth. The phosphorylated target of STK3 was revealed by co-immunoprecipitation and in vitro kinase assays. STK3-targeted drugs were screened out by molecular docking and cellular thermal shift assay (CETSA).ResultsReduction of YAP1 significantly impaired STK3 expression at both mRNA and protein levels, and deletion of STK3 partially attenuated the oncogenic activity of YAP1. Notably, MNNG-induced tumors in Yap1-/-Taz-/- mice exhibited decreased STK3 expression. Knockdown of STK3 led to reduced expression of stemness markers and xenograft growth, while sensitizing GC organoids and xenografts to 5-fluorouracil treatment. Mechanistically, the direct interaction between STK3 and GSK-3β promoted GSK-3β phosphorylation and β-catenin nuclear accumulation, and thus the activation of Wnt signaling. Furthermore, aminopterin demonstrates as a promising STK3-targeted small molecule with remarkable effectiveness in inhibiting GC cell malignance and xenograft growth.ConclusionsSTK3 was identified as a transcriptional target of YAP1, leading to enhanced DNA repair ability and stemness acquisition during GC progression by activating Wnt/β-catenin activity through GSK-3β degradation. Moreover, STK3-targeted therapy offered a novel approach to concur acquired chemo-resistance in GC patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40604818 · DOI · PMC12220525
Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling [2]
Abstract reading summary — source excerpts
- Opening excerpt
- CTNNB1, the gene encoding β-catenin, is a frequent target for oncogenic mutations activating the canonical Wnt signaling pathway, typically through missense mutations within a degron hotspot motif in exon 3.
- Closing excerpt
- Our work provides a resource to understand mutational diversity within a pan-cancer mutation hotspot, with potential implications for targeted therapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
CTNNB1, the gene encoding β-catenin, is a frequent target for oncogenic mutations activating the canonical Wnt signaling pathway, typically through missense mutations within a degron hotspot motif in exon 3. Here, we combine saturation genome editing with a fluorescent reporter assay to quantify signaling phenotypes for all 342 possible missense mutations in the mutation hotspot. Our data define the genetic requirements for β-catenin degron function, refine the consensus motif for substrate recognition by β-TRCP and reveal diverse levels of signal activation among known driver mutations. Tumorigenesis in different human tissues involves selection for CTNNB1 mutations spanning distinct ranges of predicted activity. In hepatocellular carcinoma, mutation effect scores distinguish two tumor subclasses with different levels of β-catenin signaling, and weaker mutations predict greater immune cell infiltration in the tumor microenvironment. Our work provides a resource to understand mutational diversity within a pan-cancer mutation hotspot, with potential implications for targeted therapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41629672 · DOI · PMC12900645
Preventive Effect of Fisetin on Follicular Granulosa Cells Senescence via Attenuating Oxidative Stress and Upregulating the Wnt/β-Catenin Signaling Pathway [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Oxidative stress-mediated dysfunction of granulosa cells (GCs) is recognized as a pivotal driver of prehierarchical follicular atresia in poultry, contributing substantially to the reduced egg production in aged laying hens.
- Closing excerpt
- These findings indicate that fisetin prevents follicular atresia by suppressing GCs oxidative damage and improving cell cycle arrest via activating the Nrf2/HO-1 and Wnt/β-catenin signaling pathways.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (230 words)
Oxidative stress-mediated dysfunction of granulosa cells (GCs) is recognized as a pivotal driver of prehierarchical follicular atresia in poultry, contributing substantially to the reduced egg production in aged laying hens. Here, we investigated the protective effects of the natural flavonol, fisetin, on aged chicken follicular GCs. A D-galactose (D-gal)-induced aging model of GCs was established to evaluate the protective role of fisetin against cellular senescence. Small yellow follicles (SYFs) from 580-day-old hens were cultured with fisetin for 72 h to verify its ameliorative effect on naturally aged follicles. Fisetin reduced the typical characteristic of senescence in D-gal-induced GCs, as reflected by decreased senescence-associated β-galactosidase (SA-β-gal) activity and increased expression of proliferation-related proteins, including cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 1 (CDK1), and Cyclin B1. Furthermore, fisetin enhanced the activity of antioxidant enzymes by activating the Nrf2/HO-1 signaling pathways, while attenuating mitochondrial dysfunction and promoting ATP production in senescent GCs. Additionally, fisetin significantly promoted nuclear translocation of β-catenin, and suppressed the expression of senescence marker proteins p53 and p21, thereby alleviating cell cycle arrest in D-gal-induced senescent GCs. Simultaneous inhibition of Nrf2/HO-1 and β-catenin signaling also abolished the beneficial effects of fisetin on oxidative stress and cell proliferation in naturally senescent follicles. These findings indicate that fisetin prevents follicular atresia by suppressing GCs oxidative damage and improving cell cycle arrest via activating the Nrf2/HO-1 and Wnt/β-catenin signaling pathways.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41227350 · DOI · PMC12610666
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities [4]
- Research article Targeting the Wnt/β-catenin signaling pathway in cancer [5]
- Research article Wnt/β-catenin signaling in cancers and targeted therapies [6]
- Research article Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities [7]
- Research article The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators [8]
- Research article WNT-β-catenin signalling - a versatile player in kidney injury and repair [9]
References
- Xie F, Lyu Y, Chen B, Leung HW, Yu P, Feng T, et al.. STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis. . 2025. PMID 40604818 · DOI · PMC12220525
- Krishna A, Meynert A, Dolt KS, Kelder M, Mesropian A, Ewing A, et al.. Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling. . 2026. PMID 41629672 · DOI · PMC12900645
- Dong J, Yang Z, Yuan Q, Zeng W, Mi Y, Zhang C. Preventive Effect of Fisetin on Follicular Granulosa Cells Senescence via Attenuating Oxidative Stress and Upregulating the Wnt/β-Catenin Signaling Pathway. . 2025. PMID 41227350 · DOI · PMC12610666
- Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, et al.. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther. 2022. PMID 34980884 · DOI · PMC8724284
- Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol. 2020. PMID 33276800 · DOI · PMC7716495
- Yu F, Yu C, Li F, Zuo Y, Wang Y, Yao L, et al.. Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther. 2021. PMID 34456337 · DOI · PMC8403677
- Xu X, Zhang M, Xu F, Jiang S. Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities. Mol Cancer. 2020. PMID 33234169 · DOI · PMC7686704
- Rim EY, Clevers H, Nusse R. The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators. Annu Rev Biochem. 2022. PMID 35303793 · DOI
- Schunk SJ, Floege J, Fliser D, Speer T. WNT-β-catenin signalling - a versatile player in kidney injury and repair. Nat Rev Nephrol. 2021. PMID 32989282 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.