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Sur I, Zhao W, Zhang J, Kling Pilström M, Webb AT, Cheng H, Ristimäki A, Katajisto P, Enge M, Rannikmae H, de la Roche M, Taipale J
Life Sci. Alliance 8 (6) - [2025-06-00; online 2025-04-03]
Cancer has been characterized as a wound that does not heal. Malignant cells are morphologically distinct from normal proliferating cells but have extensive similarities to tissues undergoing wound healing and/or regeneration. The mechanistic basis of this similarity has, however, remained enigmatic. Here, we show that the genomic region upstream of Myc, which carries more cancer susceptibility in humans than any other genomic region, is required for intestinal regeneration after radiation damage. Failure to regenerate is associated with inefficient Ly6a/Sca1+ stem/progenitor cell mobilization, and almost complete failure to re-establish Lgr5+ cell compartment in the intestinal crypts. The Myc upstream region is also critical for growth of adult intestinal cells in 3D organoid culture. We show that culture conditions recapitulating most aspects of adult normal tissue architecture still reprogram normal cells to proliferate using a mechanism similar to that employed by cancer cells. Our results establish a function for the Myc super-enhancer region as the genetic link between tissue regeneration and tumorigenesis, and demonstrates that normal tissue renewal and regeneration of tissues after severe damage are mechanistically distinct.2-540
NGI Stockholm (Genomics Applications) [Service]
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 40180576
DOI 10.26508/lsa.202403090
Crossref 10.26508/lsa.202403090
pmc: PMC11969384
pii: 8/6/e202403090