ArticleDisease models & mechanisms2014
Oncogenic mutations in adenomatous polyposis coli (Apc) activate mechanistic target of rapamycin complex 1 (mTORC1) in mice and zebrafish.
Article in Disease models & mechanisms, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 29 citations in OpenAlex.
- miR-452-3p Targets Adenomatous Polyposis Coli to Regulate the Malignant Phenotypes and Prognosis of Esophageal Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- Review
- The Tumor SuppressorJournal of developmental biology · 2023Article
- Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture.Scientific reports · 2021Article
- Lithium and Therapeutic Targeting of GSK-3.Cells · 2021Review
- Zebrafish Cancer Predisposition Models.Frontiers in cell and developmental biology · 2021Review
- Are Wnt/β-Catenin and PI3K/AKT/mTORC1 Distinct Pathways in Colorectal Cancer?Cellular and molecular gastroenterology and hepatology · 2020Review
- Loss of adenomatous polyposis coli function renders intestinal epithelial cells resistant to the cytokine IL-22.PLoS biology · 2019Article
- Role of mTORC1 in intestinal epithelial repair and tumorigenesis.Cellular and molecular life sciences : CMLS · 2019Review
- Functional characterization ofOncotarget · 2019Article
- Article
- Regulation of Osteoblast Metabolism by Wnt Signaling.Endocrinology and metabolism (Seoul, Korea) · 2018Review
- Article
- Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing.The Journal of biological chemistry · 2017Article
- Wnt Signaling in Normal and Malignant Stem Cells.Current stem cell reports · 2016Article
- The mTOR pathway in obesity driven gastrointestinal cancers: Potential targets and clinical trials.BBA clinical · 2016Review
- Type I Interferons Control Proliferation and Function of the Intestinal Epithelium.Molecular and cellular biology · 2016Article
- The lure of zebrafish in liver research: regulation of hepatic growth in development and regeneration.Current opinion in genetics & development · 2015Review
- TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis.Oncoscience · 2015Article
- Mechanistic target of rapamycin complex 1 signaling regulates cell proliferation, cell survival, and differentiation in regenerating zebrafish fins.BMC developmental biology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Truncating mutations in adenomatous polyposis coli (APC) are strongly linked to colorectal cancers. APC is a negative regulator of the Wnt pathway and constitutive Wnt activation mediated by enhanced Wnt-β-catenin target gene activation is believed to be the predominant mechanism responsible for APC mutant phenotypes. However, recent evidence suggests that additional downstream effectors contribute to APC mutant phenotypes. We previously identified a mechanism in cultured human cells by which APC, acting through glycogen synthase kinase-3 (GSK-3), suppresses mTORC1, a nutrient sensor that regulates cell growth and proliferation. We hypothesized that truncating Apc mutations should activate mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes. We find that mTORC1 is strongly activated in apc mutant zebrafish and in intestinal polyps in Apc mutant mice. Furthermore, mTORC1 activation is essential downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes including early lethality, reduced circulation and liver hyperplasia. Importantly, combining mTORC1 and Wnt inhibition rescues defects in morphogenesis of the anterior-posterior axis that are not rescued by inhibition of either pathway alone. These data establish mTORC1 as a crucial, β-catenin independent effector of oncogenic Apc mutations and highlight the importance of mTORC1 regulation by APC during embryonic development. Our findings also suggest a new model of colorectal cancer pathogenesis in which mTORC1 is activated in parallel with Wnt/β-catenin signaling.
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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.