ArticlePLoS genetics2015
Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Beyond Rodents: Alternative Animal Models in Colorectal Cancer Research.International journal of molecular sciences · 2025Review
- 4-HIAA Blocks Methamphetamine-Induced Conditioned Place Preference in Mice Through Modulation of the 5-HT Pathway in the Nucleus Accumbens.Addiction biology · 2025Article
- Epithelial cell-fate switch triggering ectopic ligand-receptor-mediated JAK-STAT signaling promotes tumorigenesis iniScience · 2025Article
- Robustness and variability inbioRxiv : the preprint server for biology · 2024Article
- GPR35 and mediators from platelets and mast cells in neutrophil migration and inflammation.Immunological reviews · 2023Review
- Caenorhabditis elegans for research on cancer hallmarks.Disease models & mechanisms · 2023Article
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- Tissue-specific inhibition of protein sumoylation uncovers diverse SUMO functions during C. elegans vulval development.PLoS genetics · 2022Article
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- From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation.Trends in genetics : TIG · 2021Review
- The genetics of gene expression in a Caenorhabditis elegans multiparental recombinant inbred line population.G3 (Bethesda, Md.) · 2021Article
- Xenobiotic metabolism and transport inJournal of toxicology and environmental health. Part B, Critical reviews · 2021Review
- Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans.PLoS genetics · 2020Article
- Metabolite sensing and signaling in cancer.The Journal of biological chemistry · 2020Review
- The GeneG3 (Bethesda, Md.) · 2020Article
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- Dissecting the eQTL Micro-Architecture inFrontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes. While many of the tumor initiating mutations are well characterized, the effect of genetic background variation on disease onset and progression is less understood. We have used C. elegans genetics to identify genetic modifiers of the oncogenic RAS/MAPK signaling pathway. Quantitative trait locus analysis of two highly diverged C. elegans isolates combined with allele swapping experiments identified the polymorphic monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of RAS/MAPK signaling. We further show that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is a product of MAOA catalysis, systemically inhibits RAS/MAPK signaling in different organs of C. elegans. Thus, MAOA activity sets a global threshold for MAPK activation by controlling 5-HIAA levels. To our knowledge, 5-HIAA is the first endogenous small molecule that acts as a systemic inhibitor of RAS/MAPK signaling.
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Registered trials
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.