ArticleCell death & disease2021
Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Engineering a Human-Sized Common Bile Duct Prototype with Regenerative Potential: In Vitro Evaluation of Mechanics, Function, Degradation, and Immune Modulation.Advanced healthcare materials · 2025Article
- The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.Frontiers in immunology · 2025Review
- The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase.Microbial cell factories · 2024Article
- Prognostic value of amino acid metabolism-related gene expression in invasive breast carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Integrated multi-omics of the gastrointestinal microbiome and ruminant host reveals metabolic adaptation underlying early life development.Microbiome · 2022Article
- L-arginine metabolism as pivotal interface of mutual host-microbe interactions in the gut.Gut microbesReview
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.
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Registered trials
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