ArticleOncogene2017
Targeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells.British journal of cancer · 2026Article
- From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network-based pharmacological and cellular assay.Frontiers in pharmacology · 2024Article
- PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediatedInternational journal of biological sciences · 2023Article
- Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022Article
- Toward Understanding the Mechanisms of Malignant Peripheral Nerve Sheath Tumor Development.International journal of molecular sciences · 2021Review
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- New Horizons: Emerging Therapies and Targets in Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2021Review
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- PAK1 Mediates Bone Marrow Stromal Cell-Induced Drug Resistance in Acute Myeloid Leukemia via ERK1/2 Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- p21-Activated Kinase 1 Promotes Breast TumorigenesisFrontiers in cell and developmental biology · 2021Article
- The effects of mutant Ras proteins on the cell signalome.Cancer metastasis reviews · 2020Review
- Targeting Rho GTPase Signaling Networks in Cancer.Frontiers in cell and developmental biology · 2020Review
- CDK12 and PAK2 as novel therapeutic targets for human gastric cancer.Theranostics · 2020Article
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
- Pyrido[2,3-Molecules (Basel, Switzerland) · 2019Review
- Targeting p21-activated kinase 1 inhibits growth and metastasis via Raf1/MEK1/ERK signaling in esophageal squamous cell carcinoma cells.Cell communication and signaling : CCS · 2019Article
- C14orf159 suppresses gastric cancer cells' invasion and proliferation by inactivating ERK signaling.Cancer management and research · 2019Article
- Germline and SomaticCancer prevention research (Philadelphia, Pa.) · 2018Article
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs. In this study we found a strong positive correlation between the activity of PAK1/2/3 and the stage of human MPNSTs. We determined that reducing Group I Pak activity diminished MPNST cell proliferation and motility, and that these effects were not accompanied by significant blockade of the Raf/Mek/Erk pathway, but rather by reductions in Akt and β-catenin activity. Using the small molecule PAK1/2/3 inhibitor Frax1036 and the MEK1/2 inhibitor PD0325901, we showed that the combination of these two agents synergistically inhibited MPNST cell growth in vitro and dramatically decreased local and metastatic MPNST growth in animal models. Taken together, these data provide new insights into MPNST signaling deregulation and suggest that co-targeting of PAK1/2/3 and MEK1/2 may be effective in the treatment of patients with MPNSTs.
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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.