ArticleGastroenterology2022
An Enhancer-Driven Stem Cell-Like Program Mediated by SOX9 Blocks Intestinal Differentiation in Colorectal Cancer.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
- Gut microbial community and host intestinal gene expression with combined fish oil and soluble corn fiber compared with corn oil and maltodextrin: A randomized crossover trial in healthy older individuals.The American journal of clinical nutrition · 2025Trial
- Stemness in Colon Cancer.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Methylation-Associated Differentiation Features Define Biological and Prognostic Heterogeneity in CMS4 Colorectal Cancer.International journal of molecular sciences · 2026Article
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
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- RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability and inhibiting H3K18 lactylation.Cell death & disease · 2026Article
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Dynamic distribution of Paneth cells in pig intestine under normal and infection conditions.BMC veterinary research · 2026Article
- Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy.Cancer gene therapy · 2026Review
- Novel Syngeneic Cell Lines for Studying High-Risk BRAFV600E-Driven Colorectal Cancer In Vivo.Cancer research communications · 2026Article
- Chemical Perturbations Impacting Histone Acetylation Govern Colorectal Cancer Differentiation.Gastroenterology · 2026Article
- Article
- Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features.International journal of cancer · 2025Article
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Integrative single-cell transcriptomic analysis deciphers heterogeneous characteristics of gastrointestinal tract cancer.Clinical and translational medicine · 2025Article
- Uncovering key markers and therapeutic targets for renal fibrosis in diabetic kidney disease through bulk and single-cell RNA sequencing.Journal of translational medicine · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction.The Journal of clinical investigation · 2025Article
- Multiomic spatial atlas shows deleted in malignant brain tumors 1 (DMBT1) glycoprotein is lost in colonic dysplasia.The Journal of pathology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsGenomic alterations that encourage stem cell activity and hinder proper maturation are central to the development of colorectal cancer (CRC). Key molecular mediators that promote these malignant properties require further elucidation to galvanize translational advances. We therefore aimed to characterize a key factor that blocks intestinal differentiation, define its transcriptional and epigenetic program, and provide preclinical evidence for therapeutic targeting in CRC.
methodsIntestinal tissue from transgenic mice and patients were analyzed by means of histopathology and immunostaining. Human CRC cells and neoplastic murine organoids were genetically manipulated for functional studies. Gene expression profiling was obtained through RNA sequencing. Histone modifications and transcription factor binding were determined with the use of chromatin immunoprecipitation sequencing.
resultsWe demonstrate that SRY-box transcription factor 9 (SOX9) promotes CRC by activating a stem cell-like program that hinders intestinal differentiation. Intestinal adenomas and colorectal adenocarcinomas from mouse models and patients demonstrate ectopic and elevated expression of SOX9. Functional experiments indicate a requirement for SOX9 in human CRC cell lines and engineered neoplastic organoids. Disrupting SOX9 activity impairs primary CRC tumor growth by inducing intestinal differentiation. By binding to genome wide enhancers, SOX9 directly activates genes associated with Paneth and stem cell activity, including prominin 1 (PROM1). SOX9 up-regulates PROM1 via a Wnt-responsive intronic enhancer. A pentaspan transmembrane protein, PROM1 uses its first intracellular domain to support stem cell signaling, at least in part through SOX9, reinforcing a PROM1-SOX9 positive feedback loop.
conclusionsThese studies establish SOX9 as a central regulator of an enhancer-driven stem cell-like program and carry important implications for developing therapeutics directed at overcoming differentiation defects in CRC.
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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.