ArticleJournal of translational medicine2024
Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- Intratumoral Microorganisms in Tumors: Current Understanding and Emerging Therapeutic Strategies.MedComm · 2026Review
- Microbial metabolic profiling reshapes NF-κB-mediated immune metabolic network: a new mechanism for CRC development.Journal of translational medicine · 2026Review
- Gut Microbial Metabolism in Colorectal Cancer.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Pan-cancer analysis identifies LMBR1L as a prognostic and immunological biomarker with validation in colorectal cancer.European journal of medical research · 2025Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- The role of gut microbiome in colorectal cancer development: a comprehensive analysis based on metabolomics and immunomodulatory mechanisms.Frontiers in oncology · 2025Review
- Unravelling molecular mechanism of oral squamous cell carcinoma and genetic landscape: an insight into disease complexity, available therapies, and future considerations.Frontiers in immunology · 2025Review
- Comparative Analysis of Commercial and Home-Made Media on RSPO1/S6R Axis in Organoids with Different Wnt Backgrounds: A Methodological Guide for the Selection of Intestinal Patient-Derived Organoids Culture Media.International journal of molecular sciences · 2024Article
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17 authors.
Funding
Abstract
backgroundWnt/β-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis.
methodsProteins and target genes of both pathways were analysed by RT-qPCR and IHC in tissues from healthy faecal immunochemical test positive (FIT+, n = 17), FAP (n = 17) and CRC (n = 15) subjects. CRC-related mutations were analysed through NGS and Sanger. Oral, faecal and mucosal microbiota was profiled by 16 S rRNA-sequencing.
resultsWe found simultaneous hyperactivation of Wnt/β-catenin and PI3K/mTOR pathways in FAP-lesions compared to CRCs. Wnt/β-catenin molecular markers positively correlated with Clostridium_sensu_stricto_1 and negatively with Bacteroides in FAP faecal microbiota. Alistipes, Lachnospiraceae, and Ruminococcaceae were enriched in FAP stools and adenomas, the latter also showing an overabundance of Lachnoclostridium, which positively correlated with cMYC. In impaired-mTOR-mutated CRC tissues, p-S6R correlated with Fusobacterium and Dialister, the latter also confirmed in the faecal-ecosystem.
conclusionsOur study reveals an interplay between Wnt/β-catenin and PI3K/mTOR, whose derangement correlates with specific microbiota signatures in FAP and CRC patients, and identifies new potential biomarkers and targets to improve CRC prevention, early adenoma detection and treatment.
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