ArticleCancers2022
Targeting Wnt/β-Catenin Signaling by TET1/FOXO4 Inhibits Metastatic Spreading and Self-Renewal of Cancer Stem Cells in Gastric Cancer.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- CircROR1 binds HNRNPL to regulate FOXO4 pre-mRNA splicing, promoting cutaneous melanoma metastasis and serving as a therapeutic target via RNAi-loaded PEG-LNPs.Molecular cancer · 2026Article
- Smurf1 promotes gastric cancer progression by regulating Axin2-dependent Wnt signaling pathway.Scientific reports · 2025Article
- Identification and validation of RAS signaling-related genes for prognostic prediction and immunological characterization in gastric cancer.Translational cancer research · 2025Article
- Evolutionary and structural insights into DNMTs and TETs: decoding their functional heterogeneity and oncogenic roles in methylation regulation.BMC molecular and cell biology · 2025Article
- TET1 functions as a tumor suppressor in lung adenocarcinoma through epigenetic remodeling and immune modulation.Epigenetics & chromatin · 2025Article
- Role of the TGF-β/Smad3 pathway in pancreatic cancer cell growth and stem cell characteristics.Discover oncology · 2025Article
- Wnt Signaling and Circular RNAs in Esophageal and Gastric Cancers: Opportunities for Early Detection and Targeted Therapy.Journal of clinical medicine · 2025Review
- Decoding the role of cancer stem cells in digestive tract tumors: Mechanisms and therapeutic implications (Review).International journal of oncology · 2025Review
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
- KHSRP promotes cancer stem cell maintenance, tumorigenesis, and suppresses anti-tumor immunity in gastric cancer.Oncology research · 2025Article
- Targeting the Wnt/β-catenin pathway and epithelial-mesenchymal transition in gastric cancer: mechanisms, therapeutic strategies, and clinical challenges.Frontiers in oncology · 2025Review
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.Cell death and differentiation · 2024Article
- LINC01089 in cancer: multifunctional roles and therapeutic implications.Journal of translational medicine · 2024Review
- Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics.Cancer metastasis reviews · 2023Review
- Targeting the Vulnerabilities of Oncogene Activation.Cancers · 2023Article
- Review
- Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer.Biomedicines · 2023Article
- 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress.Open life sciences · 2023Article
- YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.Stem cells international · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Metastasis is the main cause of death for patients suffering gastric cancer. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critical attributes of metastasis, both of which are regulated tightly by DNA methylation and Wnt/β-catenin signaling. Here, we studied the functions of DNA dioxygenase TET1 in regulating Wnt signaling and in gastric cancer metastasis. Knocking-down and overexpressing TET1 in gastric cancer cells promoted and inhibited metastatic spreading to the liver in immune-deficient mice, respectively. TET1 showed inhibitory effects on metastasis-related features -EMT and CSC, which were reversed by interfering with Wnt/β-catenin signaling. RNA-sequencing identified FOXO4 as a direct transactivating target of TET1. FOXO4 directly interacted with β-catenin and recruited it in the cytoplasm, so as to inhibit β-catenin-mediated transcription of Wnt target genes, including CSC marker EpCAM. Moreover, modulation of FOXO4 could reverse the effects of TET1 manipulation on EMT and self-renewal of CSCs. The analysis with clinical samples confirmed the value of FOXO4 as an independent prognostic predictor of patients' overall survival. Taken together, regulation of Wnt signaling by TET1/FOXO4 is essential for metastasis-associated cellular properties, and targeting TET1/FOXO4/β-catenin pathway may serve as promising therapeutics in the prevention and treatment of gastric cancer metastasis.
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Registered trials
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