ArticleGut2015
Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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.
The trial behind it
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Who cites it
72 citing papers in PubMed, 124 citations in OpenAlex.
- Methylation array signals are predictive of chronological age without bisulfite conversion.GeroScience · 2026Article
- Alternatively activated macrophages cause DNA damage through an arginase 1-mediated bystander effect and promote epithelial cell transformation.Oncogenesis · 2026Article
- Intratumoral microbiome and pancreatic cancer: an enabling hallmark and path to novel treatments?British journal of cancer · 2026Review
- Enterococcus faecalis-induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition.Cell communication and signaling : CCS · 2026Article
- Emerging risk factors and the role of gut microbiota in immunomodulation and therapeutic implications in colorectal cancer.Cancer pathogenesis and therapy · 2026Review
- The gut microbiota: an emerging modulator of drug resistance in hepatocellular carcinoma.Gut microbes · 2025Review
- Inactivation of glutathioneGut microbes · 2025Article
- Tumor necrosis factor promotes doublecortin-like kinase 1 expression and cellular reprogramming in intestinal epithelial cells leading to neoplastic transformation.Cell communication and signaling : CCS · 2025Article
- LY6E as a new prognostic biomarker of multiple myeloma-related bone disease.Scientific reports · 2025Article
- Unraveling the Complexities of Myeloid-Derived Suppressor Cells in Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Fusobacterium nucleatum promotes colorectal cancer through neogenesis of tumor stem cells.The Journal of clinical investigation · 2025Article
- Long-chain polyunsaturated fatty acids influence colorectal cancer progression via the interactions between the intestinal microflora and the macrophages.Molecular and cellular biochemistry · 2024Review
- Cancer stem cells: advances in the glucose, lipid and amino acid metabolism.Molecular and cellular biochemistry · 2024Review
- Network dynamics and therapeutic aspects of mRNA and protein markers with the recurrence sites of pancreatic cancer.Heliyon · 2024Article
- Review
- The pathogenicity of vancomycin-resistant Enterococcus faecalis to colon cancer cells.BMC infectious diseases · 2024Article
- Postbiotics in colorectal cancer: intervention mechanisms and perspectives.Frontiers in microbiology · 2024Review
- Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention.Frontiers in oncology · 2024Review
- Epithelial-mesenchymal interaction protects normal colonocytes from 4-HNE-induced phenotypic transformation.PloS one · 2024Article
- Genomic and epigenomic integrative subtypes of renal cell carcinoma in a Japanese cohort.Nature communications · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCommensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect.
designPrimary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)-an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis.
resultsPrimary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice.
conclusionsThese results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect.
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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.