ArticleGut2015
Activation of β-catenin signalling by TFF1 loss promotes cell proliferation and gastric tumorigenesis.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Probiotics ameliorate H. pylori-associated gastric β-catenin and COX-2 carcinogenesis signaling by regulating miR-185.Journal of biomedical science · 2025Trial
- Article
- Yin Yang 1 activates JAK-STAT3-mediated epithelial-mesenchymal transition inWorld journal of clinical oncology · 2025Article
- Aging-associated ZNF573 methylation regulates RNF19B-PIK3CA ubiquitination to promote prostate cancer.Oncogene · 2025Article
- Interdependency of estradiol-mediated ERα activation and subsequent PR and GREB1 induction to control cell cycle progression.Heliyon · 2024Article
- Helicobacter pylori promotes gastric cancer progression by activating the TGF-β/Smad2/EMT pathway through HKDC1.Cellular and molecular life sciences : CMLS · 2024Article
- Spatial analyses revealed S100P + TFF1 + tumor cells in spread through air spaces samples correlated with undesirable therapy response in non-small cell lung cancer.Journal of translational medicine · 2024Article
- DRD4 promotes chemo-resistance and cancer stem cell-like phenotypes by mediating the activation of the Akt/β-catenin signaling axis in liver cancer.British journal of cancer · 2024Article
- The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage.Cell communication and signaling : CCS · 2024Article
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
- LASS2 enhances chemosensitivity to cisplatin by inhibiting PP2A-mediated β-catenin dephosphorylation in a subset of stem-like bladder cancer cells.BMC medicine · 2024Article
- Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer.Archives of microbiology · 2023Review
- Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach.Genomics & informatics · 2023Article
- CDK1 bridges NF-κB and β-catenin signaling in response to H. pylori infection in gastric tumorigenesis.Cell reports · 2023Article
- A Novel Prognostic Marker and Therapeutic Target Associated with Glioma Progression in a Tumor Immune Microenvironment.Journal of inflammation research · 2023Article
- Kruppel-like factor 13 inhibits cell proliferation of gastric cancer by inducing autophagic degradation of β-catenin.Discover oncology · 2022Article
- Glypican 1 promotes proliferation and migration in esophagogastric adenocarcinoma via activating AKT/GSK/β-catenin pathway.Journal of gastrointestinal oncology · 2022Article
- circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer.Molecular cancer · 2022Article
- Self-Renewal and Cancers of the Gastric Epithelium: An Update and the Role of the Lectin TFF1 as an Antral Tumor Suppressor.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectiveIn this study, we investigated the role of Trefoil factor 1 (TFF1) in regulating cell proliferation and tumour development through β-catenin signalling using in vivo and in vitro models of gastric tumorigenesis.
designTff1-knockout (Tff1-KO) mice, immunohistochemistry, luciferase reporter, qRT-PCR, immunoblot, and phosphatase assays were used to examine the role of TFF1 on β-catenin signalling pathway.
resultsNuclear localisation of β-catenin with transcriptional upregulation of its target genes, c-Myc and Ccnd1, was detected in hyperplastic tissue at an early age of 4-6 weeks and maintained during all stages of gastric tumorigenesis in the Tff1-KO mice. The reconstitution of TFF1 or TFF1 conditioned media significantly inhibited the β-catenin/T-cell factor (TCF) transcription activity in MKN28 gastric cancer cells. In agreement with these results, we detected a reduction in the levels of nuclear β-catenin with downregulation of c-MYC and CCND1 mRNA. Analysis of signalling molecules upstream of β-catenin revealed a decrease in phosphorylated glycogen synthase kinase 3β (p-GSK3β) (Ser9) and p-AKT (Ser473) protein levels following the reconstitution of TFF1 expression; this was consistent with the increase of p-β-catenin (Ser33/37/Thr41) and decrease of p-β-catenin (Ser552). This TFF1-induced reduction in phosphorylation of GSK3β, and AKT was dependent on protein phosphatase 2A (PP2A) activity. The treatment with okadaic acid or knockdown of PP2A abrogated these effects. Consistent with the mouse data, we observed loss of TFF1 and an increase in nuclear localisation of β-catenin in stages of human gastric tumorigenesis.
conclusionsOur data indicate that loss of TFF1 promotes β-catenin activation and gastric tumorigenesis through regulation of PP2A, a major regulator of AKT-GSK3β signalling.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.