ArticleThe Journal of clinical investigation2018
Wnt signaling suppresses MAPK-driven proliferation of intestinal stem cells.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed.
- The anti-diarrheal role of iron in piglets: Regulation of colonic goblet cell function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Impact of non-genetic heterogeneity of BRAF-mutant colon cancer organoids on growth kinetics, drug sensitivity and Wnt dynamics.International journal of cancer · 2026Article
- A high-MAPK, low-WNT cell state drives metastatic dissemination in colorectal cancer.Nature cancer · 2026Article
- Dynamic transitioning between MAPK-driven and WNT-driven cell states drives intestinal cancer and shapes therapy response.Nature genetics · 2026Article
- Article
- DHX15 overexpression suppresses colorectal cancer cell line proliferation.Oncology letters · 2026Article
- Loss of inducible nitric oxide synthase promotes Kras/Pten-driven lung tumorigenesis.Frontiers in cell and developmental biology · 2026Article
- Intestinal stem and progenitor cells exhibit distinct adaptive responses to inflammatory stress in IBD.Stem cell research & therapy · 2025Article
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- Adiponectin Regulated by Indole-3-Acetic Acid in Paneth Cells Controls Renewal and Differentiation of Gut Stem Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Noninvasive Therapeutic Monitoring of Circulating Tumor DNA in BRAF-Mutant Metastatic Colon Cancer Using Droplet Digital PCR, Next-Generation Sequencing, and Fragmentomics.Case reports in oncological medicine · 2025Article
- Comprehensive analysis of the functional and immunological significance of ETV4 in pan-cancer and its validation in digestive tumors.Frontiers in immunology · 2025Article
- Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway inFrontiers in cell and developmental biology · 2025Article
- FAK loss reduces BRAFeLife · 2024Article
- Review
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/β-catenin to RTK/MAPK signaling.The Journal of clinical investigation · 2024Article
- Death receptor 5 is required for intestinal stem cell activity during intestinal epithelial renewal at homoeostasis.Cell death & disease · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Intestinal homeostasis depends on a slowly proliferating stem cell compartment in crypt cells, followed by rapid proliferation of committed progenitor cells in the transit amplifying (TA) compartment. The balance between proliferation and differentiation in intestinal stem cells (ISCs) is regulated by Wnt/β-catenin signaling, although the mechanism remains unclear. We previously targeted PORCN, an enzyme essential for all Wnt secretion, and demonstrated that stromal production of Wnts was required for intestinal homeostasis. Here, a PORCN inhibitor was used to acutely suppress Wnt signaling. Unexpectedly, the treatment induced an initial burst of proliferation in the stem cell compartment of the small intestine, due to conversion of ISCs into TA cells with a loss of intrinsic ISC self-renewal. This process involved MAPK pathway activation, as the proliferating cells in the base of the intestinal crypt contained phosphorylated ERK1/2, and a MEK inhibitor attenuated the proliferation of ISCs and their differentiation into TA cells. These findings suggest a role for Wnt signaling in suppressing the MAPK pathway at the crypt base to maintain a pool of ISCs. The interaction between Wnt and MAPK pathways in vivo has potential therapeutic applications in cancer and regenerative medicine.
Indexed as
Identifiers
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.