ArticleNature communications2025
p53 protein degradation redefines the initiation mechanisms and drives transitional mutations in colorectal cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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
5 citing papers in PubMed.
- The germline landscape of pituitary adenomas: established and emerging predisposition genes.The Journal of clinical endocrinology and metabolism · 2026Review
- Combinatorial post-translational modification reprogramming of the endomembrane system in colorectal cancer.Translational cancer research · 2026Article
- Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Incidence of colorectal cancer (CRC) is increasing likely due to different mechanisms driving initiation and progression. The initial model proposed by Fearon and Vogelstein posits it as a multi-hit neoplasia, originating from adenomatous-polyps induced by WNT activation, ultimately progressing to aggressiveness through p53 loss. Integrating human data with mouse genetics, we redefine this paradigm, highlighting pivotal roles of MYC, oncogenic URI and p53 degradation to initiate CRC. Early APC loss activates MYC to transcriptionally upregulate URI, which modulates MDM2 activity, triggering p53 proteasomal degradation, essential for tumour initiation and mutation burden accrual in CRC mice. Remarkably, reinstating p53 levels via genetic URI depletion or p53 super-expression in CRC mice with WNT pathway activation prevents tumour initiation and extends lifespan. Our data reveal a "two-hit" genetic model central to APC loss-driven CRC initiation, wherein MYC/URI axis intricately controls p53 degradation, offering mechanistic insights into transitional mutation acquisition essential for CRC progression.
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