ArticleGastroenterology2013
Foxf2 in intestinal fibroblasts reduces numbers of Lgr5(+) stem cells and adenoma formation by inhibiting Wnt signaling.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Role of the Forkhead box family protein FOXF2 in the progression of solid tumor: systematic review.Journal of cancer research and clinical oncology · 2024Pooled it
- Forkhead box F2 as a novel prognostic biomarker and potential therapeutic target in human cancers prone to bone metastasis: a meta-analysis.The Journal of international medical research · 2021Pooled it
- The Role of Fibroblast-Epithelial Cross-Talk on the Distribution of Distinct Fibroblast Phenotypes in the Intestinal Crypt.Bulletin of mathematical biology · 2026Article
- Fibroblasts modulate epithelial cell behavior within the proliferative niche and differentiated cell zone within a human colonic crypt model.Frontiers in bioengineering and biotechnology · 2024Article
- Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.Biomedicines · 2023Review
- Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.Nature communications · 2022Article
- Alcohol-induced inhibition of bone formation and neovascularization contributes to the failure of fracture healing via the miR-19a-3p/FOXF2 axis.Bone & joint research · 2022Article
- LSD1 regulates the FOXF2-mediated Wnt/β-catenin signaling pathway by interacting with Ku80 to promote colon cancer progression.American journal of cancer research · 2022Article
- Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers.Frontiers in oncology · 2022Review
- Review
- Fibroblast Subsets in Intestinal Homeostasis, Carcinogenesis, Tumor Progression, and Metastasis.Cancers · 2021Review
- The regulatory roles and mechanisms of the transcription factor FOXF2 in human diseases.PeerJ · 2021Article
- FOXF2 acts as a crucial molecule in tumours and embryonic development.Cell death & disease · 2020Review
- FOXF2 reprograms breast cancer cells into bone metastasis seeds.Nature communications · 2019Article
- FOXF2 is required for cochlear development in humans and mice.Human molecular genetics · 2019Article
- Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models.Disease models & mechanisms · 2019Review
- The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis.Molecular cancer · 2019Review
- Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by promoting apoptosis yet enabling cell junction dissolution and migration.Breast cancer research : BCR · 2018Article
- FOXF2 differentially regulates expression of metabolic genes in non-cancerous and cancerous breast epithelial cells.Trends in diabetes and metabolism · 2018Article
- FOXF2 deficiency promotes hepatocellular carcinoma metastasis by inducing mesenchymal-epithelial transition.Cancer biomarkers : section A of Disease markers · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe stem cell niche at the base of the intestinal crypts, as well as stemness and high clonogenicity in colon cancer cells, depend on Wnt signaling to β-catenin. Fibroblasts modulate the Wnt pathway in normal and neoplastic epithelial cells via unclear mechanisms. We investigated how in intestinal fibroblasts the forkhead transcription factor Foxf2 controls Wnt signaling to affect numbers of stem cells and formation and growth of adenomas in mice.
methodsWe created mice with different copy numbers of Foxf2 by generating Foxf2(-/+) mice and a transgenic strain, Tg(FOXF2). Adenoma formation was investigated in Apc(Min/+) mice, stem cells were counted in mice with the Lgr5-enhanced green fluorescent protein knock-in allele, proliferation was measured by incorporation of bromodeoxyuridine, Foxf2 and Sfrp1 were localized by immunohistochemistry, and signaling pathways were analyzed by quantitative polymerase chain reaction and immunoblot assays.
resultsEpithelial β-catenin was stabilized in Foxf2(-/+) mice, resulting in increased number and size of adenomas. Tg(FOXF2) mice, however, were partially resistant to intestinal neoplasia and developed fewer and smaller adenomas; Foxf2(-/+) mice developed 24-fold more tumors than Tg(FOXF2) mice. Epithelial cells of Foxf2(-/+) mice also had higher numbers of Lgr5(+) stem cells and greater amounts of crypt cell proliferation and expression of Myc (a target of Wnt signaling) than Tg(FOXF2) mice. Expression of Sfrp1, which encodes an extracellular inhibitor of Wnt, in fibroblasts increased with copy number of Foxf2.
conclusionsFoxf2 is a fibroblast factor that inhibits paracrine Wnt signaling and restricts the crypt stem cell niche in intestines of mice. Loss of Foxf2 promotes adenoma formation and growth.
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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.