ArticleExperimental neurology2009
PAK kinase regulates Rac GTPase and is a potential target in human schwannomas.
Article in Experimental neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases.Cancers · 2024Article
- Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Genetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Article
- Updates on Tumor Biology in Vestibular Schwannoma.Otolaryngologic clinics of North America · 2023Review
- The biological underpinnings of radiation therapy for vestibular schwannomas: Review of the literature.Laryngoscope investigative otolaryngology · 2021Review
- Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects.Frontiers in oncology · 2021Review
- Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion.Pharmacology research & perspectives · 2019Article
- Persistent Oxidative Stress in Vestibular Schwannomas After Stereotactic Radiation Therapy.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2018Article
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- Approaches of targeting Rho GTPases in cancer drug discovery.Expert opinion on drug discovery · 2015Review
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- Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival.Oncogene · 2014Article
- Group I PAK inhibitor IPA-3 induces cell death and affects cell adhesivity to fibronectin in human hematopoietic cells.PloS one · 2014Article
- BRAF activates and physically interacts with PAK to regulate cell motility.Endocrine-related cancer · 2014Article
- FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas.The Journal of biological chemistry · 2013Article
- RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis.Molecular cancer therapeutics · 2013Review
- Combined p21-activated kinase and farnesyltransferase inhibitor treatment exhibits enhanced anti-proliferative activity on melanoma, colon and lung cancer cell lines.Molecular cancer · 2013Article
- Article
- Group I p21-activated kinases (PAKs) promote tumor cell proliferation and survival through the AKT1 and Raf-MAPK pathways.Molecular cancer research : MCR · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Merlin loss causes benign tumours of the nervous system, mainly schwannomas and meningiomas. Schwannomas show enhanced Rac1 and Cdc42 activity, the p21-activated kinase 2 (PAK2) activation and increased ruffling and cell adhesion. PAK regulates activation of merlin. PAK has been proposed as a potential therapeutic target in schwannomas. However where PAK stands in the Rac pathway is insufficiently characterised. We used a novel small-molecule PAK inhibitor, IPA-3, to investigate the role of PAK activation on Rac1/Cdc42 activity, cell spreading and adhesion in human primary schwannoma and Schwann cells. We show that IPA-3 blocks activation of PAK2 at Ser192/197 that antagonises PAK's interaction with Pix. Accordingly, Pix-mediated Rac1 activation is decreased in IPA-3 treated schwannoma cells, indicating that PAK acts upstream of Rac. We show that this Rac activation at the level of focal adhesions in schwannoma cells is essential for cell spreading and adhesion in Schwann and schwannoma cells.
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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.