ArticleOncogene2010
The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology · 2019Pooled it
- Association of Activating GNAS Mutations and Outcomes with Chemotherapy in Metastatic Appendiceal Adenocarcinoma.Annals of surgical oncology · 2026Article
- Gsα deficiency in macrophages promotes tumor progression via the MAPK signaling pathway.Journal of molecular medicine (Berlin, Germany) · 2026Article
- GPA33 forms a distinct diagnostic target class to Claudin 18.2 in oesophageal adenocarcinoma enabling the development of a novel GPA33 antibody-based detection platform.Cellular & molecular biology letters · 2026Article
- Contract to kill: GNAS mutation.Molecular cancer · 2025Review
- Characterisation of aEndocrine oncology (Bristol, England) · 2025Article
- Dynamic Changes in Circulating Tumor DNA During Immunotherapy for Head and Neck Cancer: SHIZUKU-HN Study.International journal of molecular sciences · 2024Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma.Leukemia · 2024Article
- Arginines of the CGN codon family are Achilles' heels of cancer genes.Scientific reports · 2024Article
- Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.Molecular cancer research : MCR · 2024Article
- Genetic characterization of intramuscular myxomas.Pathology oncology research : POR · 2024Article
- Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma.Heliyon · 2023Article
- Activation of melanocortin-1 receptor signaling in melanoma cells impairs T cell infiltration to dampen antitumor immunity.Nature communications · 2023Article
- Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach.Genomics & informatics · 2023Article
- Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis.NPJ genomic medicine · 2023Article
- Active GαMolecular and cellular biology · 2023Article
- Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma.Frontiers in oncology · 2023Article
- Region-specific denoising identifies spatial co-expression patterns and intra-tissue heterogeneity in spatially resolved transcriptomics data.Nature communications · 2022Article
- Tubulovillous adenoma with high-grade dysplasia of the vulva harboring high tumor mutational burden and cancer-associated mutations: a case report.Diagnostic pathology · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, suggesting that mutations such as R201C may be oncogenic in these tissues. To study the role of GNAS in intestinal tumourigenesis, we placed GNAS R201C under the control of the A33-antigen promoter (Gpa33), which is almost exclusively expressed in the intestines. The GNAS R201C mutation has been shown to result in the constitutive activation of Gsalpha and adenylate cyclase and to lead to the autonomous synthesis of cyclic adenosine monophosphate (cAMP). Gpa33(tm1(GnasR201C)Wtsi/+) mice showed significantly elevated cAMP levels and a compensatory upregulation of cAMP-specific phosphodiesterases in the intestinal epithelium. GNAS R201C alone was not sufficient to induce tumourigenesis by 12 months, but there was a significant increase in adenoma formation when Gpa33(tm1(GnasR201C)Wtsi/+) mice were bred onto an Apc(Min/+) background. GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67. Furthermore, the effects of GNAS R201C on the Wnt pathway were additive to the inactivation of Apc. Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis.
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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.