ArticleNature aging2025
Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
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
5 citing papers in PubMed.
- Review
- Lactylation of GDF15 Regulates Angiogenesis in Ischemic Stroke via Activating PI3K/AKT/mTOR Pathway.Molecular neurobiology · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Morusin targeting GDF15 enhances ferroptosis and overcomes cisplatin resistance in NSCLC.Frontiers in pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
One of the most abundant cellular components of the normal adjacent tissue surrounding colorectal cancer is colonic epithelial cells (CECs); however, little is known about their interactions with tumor cells. Here we found that peritumoral CECs collaborate with cancer cells to orchestrate a pro-carcinogenic niche. In clinical cohort analyses, we show that growth differentiation factor 15 (GDF15) levels increase in normal adjacent tissue, in particular in CECs, at advanced disease and are inversely correlated with survival. Using mouse models, organoids and in vitro approaches, we link GDF15 upregulation to senescence in peritumoral CECs and identify a CEC-derived GDF15-driven metabolic feedback loop fueling tumor survival. We show that GDF15 secretion upregulates the glycolytic enzyme ENO1 in cancer cells, which triggers extracellular lactate release and subsequent lactylation of H4K8 in CECs, augmenting GDF15 transcription. Our findings establish a mode of intercellular crosstalk mediating collaboration between colorectal cancer cells and peritumoral CECs, providing a potential avenue for targeted intervention in colorectal cancer.
Indexed as
Identifiers
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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.