ArticleNature medicine2015
Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 2 of them syntheses that pooled it.
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Who cites it
161 citing papers in PubMed, 2 syntheses or guidelines pooled it, 284 citations in OpenAlex.
- Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome.Genome medicine · 2023Pooled it
- British Society of Gastroenterology position statement on serrated polyps in the colon and rectum.Gut · 2017Guideline
- A dose-finding population pharmacokinetic/pharmacodynamic model of ginisortamab, an anti-gremlin-1 monoclonal antibody, in patients with solid tumours.British journal of clinical pharmacology · 2026Article
- Dynamic Reprogramming of PDGFRA-Expressing Stromal Cells Facilitates WNT-Driven Transformation by Promoting a Fetal-Like State in the Intestinal Epithelium.Cancer research · 2026Article
- Gremlin-1 Drives Tumour Vascularization by Promoting Endothelial Differentiation and Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- Dedifferentiation-driven oncogenic stemness promotes tumor-sustaining adaptability in the intestinal epithelium.Cell death & disease · 2026Article
- Comparable expression of stem markers and damage-responsive proteins in untreated and chemoradiation-treated rectal cancer.Histology and histopathology · 2026Article
- A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C.Molecular cancer · 2026Article
- Article
- Profibrogenic Gremlin-1 expression in prostate cancer and the clinicopathologic association.Frontiers in oncology · 2026Article
- Defining the mucosal ecosystem: epithelial-mesenchymal interdependence in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- BMP antagonist CHRDL2 enhances the cancer stem-cell phenotype and increases chemotherapy resistance in colorectal cancer.Molecular oncology · 2025Article
- BMP signalling in colorectal cancer: losing the yin to WNTs yang.The Journal of pathology · 2025Review
- The Role of GREMLIN1, a Bone Morphogenetic Protein Antagonist, in Cancer Stem Cell Regulation.Cells · 2025Review
- A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.Nature cancer · 2025Article
- Integrating plasma proteome with genome reveals novel protein biomarkers in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium.bioRxiv : the preprint server for biology · 2025Article
- A comprehensive prognostic and immunological implications of Gremlin 1 in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Colorectal cancer stem cells crosstalk in tumor immune microenvironment and targeted therapeutic strategies.Frontiers in immunology · 2025Review
- Dietary and metabolic effects on intestinal stem cells in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
101 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 4 countries.
Funding
Abstract
Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.
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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.