ArticlePloS one2012
The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
- State-of-the-art in Metastatic Uveal Melanoma Treatment: A 2025 Update : How to treat Metastatic Uveal Melanoma in 2025.Current oncology reports · 2025Review
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Darovasertib, a novel treatment for metastatic uveal melanoma.Frontiers in pharmacology · 2023Review
- Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma.Frontiers of medicine · 2022Article
- Review
- Article
- Clinicopathological and prognostic significance and molecular mechanisms governing uveal melanoma.Therapeutic advances in medical oncology · 2020Review
- Emerging Therapeutic Opportunities Based on Current Knowledge of Uveal Melanoma Biology.Cancers · 2019Review
- Article
- Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma.Oncotarget · 2018Article
- P2RX7-V3 is a novel oncogene that promotes tumorigenesis in uveal melanoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.Cancer cell · 2016Article
- Dual inhibition of protein kinase C and p53-MDM2 or PKC and mTORC1 are novel efficient therapeutic approaches for uveal melanoma.Oncotarget · 2016Article
- Molecular Targeted Therapy Approaches for BRAF Wild-Type Melanoma.Current oncology reports · 2016Review
- A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.eLife · 2015Observational
- Mutations in g protein encoding genes and chromosomal alterations in primary leptomeningeal melanocytic neoplasms.Pathology oncology research : POR · 2015Article
- Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects.Brain pathology (Zurich, Switzerland) · 2015Review
- Biology of advanced uveal melanoma and next steps for clinical therapeutics.Pigment cell & melanoma research · 2015Review
- Article
- INPP4B suppresses prostate cancer cell invasion.Cell communication and signaling : CCS · 2014Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GNAQ mutations at codon 209 have been recently identified in approximately 50% of uveal melanomas (UM) and are reported to be oncogenic through activating the MAPK/Erk1/2 pathway. Protein kinase C (PKC) is a component of signaling from GNAQ to Erk1/2. Inhibition of PKC might regulate GNAQ mutation-induced Erk1/2 activation, resulting in growth inhibition of UM cells carrying GNAQ mutations. UM cells carrying wild type or mutant GNAQ were treated with the PKC inhibitor enzastaurin. Effects on proliferation, apoptosis, and signaling events were evaluated. Enzastaurin downregulated the expression of several PKC isoforms including PKCβII PKCθ, PKCε and/or their phosphorylation in GNAQ mutated cells. Downregulation of these PKC isoforms in GNAQ mutated cells by shRNA resulted in reduced viability. Enzastaurin exhibited greater antiproliferative effect on GNAQ mutant cells than wild type cells through induction of G1 arrest and apoptosis. Enzastaurin-induced G1 arrest was associated with inhibition of Erk1/2 phosphorylation, downregulation of cyclin D1, and accumulation of cyclin dependent kinase inhibitor p27(Kip1). Furthermore, enzastaurin reduced the expression of antiapoptotic Bcl-2 and survivin in GNAQ mutant cells. Inhibition of Erk1/2 phosphorylation with a MEK specific inhibitor enhanced the sensitivity of GNAQ wild type cells to enzastaurin, accompanied by p27(Kip1) accumulation and/or inhibition of enzastaurin-induced survivin and Bcl-2 upregulation. PKC inhibitors such as enzastaurin have activity against UM cells carrying GNAQ mutations through inhibition of the PKC/Erk1/2 pathway and induction of G1 arrest and apoptosis. Inhibition of the PKC pathway provides a basis for clinical investigation in patients with UM.
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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.