ArticleThe Journal of clinical investigation2013
Pak and Rac GTPases promote oncogenic KIT-induced neoplasms.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells.Cell communication and signaling : CCS · 2025Article
- Screening of potential ligands from the ZINC database with RAC1B using molecular docking and dynamics simulation analysis.Bioinformation · 2025Article
- Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms.Nature communications · 2024Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models.Frontiers in oncology · 2023Article
- Characterization of Novel Derivatives of MBQ-167, an inhibitor of the GTP-binding proteins Rac/Cdc42.Cancer research communications · 2022Article
- Characterization of the spectrum of trivalent VAV1-mutation-driven tumours using a gene-edited mouse model.Molecular oncology · 2022Article
- Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Rho guanosine nucleotide exchange factors are not such bad guys after all in cancerSmall GTPases · 2020Article
- Recent Advances in the Molecular Biology of Systemic Mastocytosis: Implications for Diagnosis, Prognosis, and Therapy.International journal of molecular sciences · 2020Review
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
- Review
- Rac GTPases in Hematological Malignancies.International journal of molecular sciences · 2018Review
- RHO GTPases in cancer: known facts, open questions, and therapeutic challenges.Biochemical Society transactions · 2018Review
- Targeting Rac and Cdc42 GTPases in Cancer.Cancer research · 2018Review
- Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer.Molecular cancer therapeutics · 2017Article
- Identifying prognostic biomarkers based on aberrant DNA methylation in kidney renal clear cell carcinoma.Oncotarget · 2017Article
- Prediction of adjuvant chemotherapy response in triple negative breast cancer with discovery and targeted proteomics.PloS one · 2017Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21-activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT.
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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.