ArticleThe Journal of clinical investigation2007
GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 116 citations in OpenAlex.
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Examining Farnesyltransferase Interaction With Cell-Permeable CaaX Peptides and the Role of the CaaX Motif in Biological Activity.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Resveratrol and N-acetylcystein reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma by inhibiting GST-pi-MAPK axis in mice.Frontiers in pharmacology · 2025Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- How cancer cells remodel lipid metabolism: strategies targeting transcription factors.Lipids in health and disease · 2021Review
- Neuronal Protein Farnesylation Regulates Hippocampal Synaptic Plasticity and Cognitive Function.Molecular neurobiology · 2021Article
- Metabolomics Analysis of Splenic CD19Frontiers in veterinary science · 2021Article
- A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis.Frontiers in immunology · 2021Article
- Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.Nature communications · 2020Article
- Small change, big effect: Taking RAS by the tail through suppression of post-prenylation carboxylmethylation.Small GTPases · 2020Review
- Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth.Developmental cell · 2020Article
- The balance of protein farnesylation and geranylgeranylation during the progression of nonalcoholic fatty liver disease.The Journal of biological chemistry · 2020Review
- Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress.The Journal of experimental medicine · 2020Article
- Review
- Increased flux through the mevalonate pathway mediates fibrotic repair without injury.The Journal of clinical investigation · 2019Article
- A Phase I Study of GGTI-2418 (Geranylgeranyl Transferase I Inhibitor) in Patients with Advanced Solid Tumors.Targeted oncology · 2019Article
- Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.Nature communications · 2019Article
- CD55 upregulation in astrocytes by statins as potential therapy for AQP4-IgG seropositive neuromyelitis optica.Journal of neuroinflammation · 2019Article
- Systemic or Forebrain Neuron-Specific Deficiency of Geranylgeranyltransferase-1 Impairs Synaptic Plasticity and Reduces Dendritic Spine Density.Neuroscience · 2018Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
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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.