ArticleOncogene2006
Histone deacetylase inhibitor FK228 suppresses the Ras-MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanoma.
Article in Oncogene, 2006. 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, 53 citations in OpenAlex.
- Histone deacetylases in the regulation of cell death and survival mechanisms in resistant BRAF-mutant cancers.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Givinostat-Liposomes: Anti-Tumor Effect on 2D and 3D Glioblastoma Models and Pharmacokinetics.Cancers · 2022Article
- Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows.Functional & integrative genomics · 2022Article
- Down-regulated HDAC3 elevates microRNA-495-3p to restrain epithelial-mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5.Journal of cellular and molecular medicine · 2020Article
- [Research Progress of Epigenetics in Pathogenesis and Treatment of Malignant Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Review
- A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions reveals that chromatin remodeling is a major mechanism inducing global changes in cancer epigenomes.BMC medical genomics · 2018Article
- Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis.International journal of molecular sciences · 2018Article
- Small Molecules Modulate Chromatin Accessibility to Promote NEUROG2-Mediated Fibroblast-to-Neuron Reprogramming.Stem cell reports · 2016Article
- Evaluation of surrogate tissues as indicators of drug activity in a melanoma skin model.Cancer medicine · 2016Article
- Treatment of resistant metastatic melanoma using sequential epigenetic therapy (decitabine and panobinostat) combined with chemotherapy (temozolomide).Cancer chemotherapy and pharmacology · 2014Article
- SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival.Journal of cellular and molecular medicine · 2014Article
- The therapeutic potential of class I selective histone deacetylase inhibitors in ovarian cancer.Frontiers in oncology · 2014Review
- HDAC inhibitors induce tumor-cell-selective pro-apoptotic transcriptional responses.Cell death & disease · 2013Article
- Histone deacetylase inhibitors enhance the apoptotic activity of insulin-like growth factor binding protein-3 by blocking PKC-induced IGFBP-3 degradation.International journal of cancer · 2012Article
- SIRT1 modulates MAPK pathways in ischemic-reperfused cardiomyocytes.Cellular and molecular life sciences : CMLS · 2012Article
- Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget · 2012Article
- Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas.The Laryngoscope · 2012Article
- Born to be alive: a role for the BCL-2 family in melanoma tumor cell survival, apoptosis, and treatment.Frontiers in oncology · 2011Article
- HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells.Leukemia · 2010Article
- F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death.Oncogene · 2010Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase (HDAC) inhibitors are expected to be effective for refractory cancer because their mechanism of action differs from that of conventional antineoplastic agents. In this study, we examined the effect of the HDAC inhibitor FK228 on malignant melanoma, as well as its molecular mechanisms. FK228 was highly effective against melanoma compared with other commonly used drugs. By comparing the gene expression profiles of melanoma cells and normal melanocytes, we defined a subset of genes specifically upregulated in melanoma cells by FK228, which included Rap1, a small GTP-binding protein of the Ras family. The expression of Rap1 mRNA and protein increased in FK228-treated melanoma cells in both a dose- and a time-dependent manner. A decrease in the phosphorylation of c-Raf, MEK1/2, and ERK1/2 was accompanied by an increase in Rap1 expression in both FK228-treated and Rap1-overexpressing cells. Inhibition of Rap1 upregulation by small interfering RNA (siRNA) abrogated the induction of apoptosis and suppression of ERK1/2 phosphorylation in FK228-treated melanoma cells. These results indicate that the cytotoxic effects of FK228 are mediated via the upregulation of Rap1. Furthermore, we found that Rap1 was overexpressed and formed a complex with B-Raf in melanoma cell lines with a V599E mutation of B-Raf. The siRNA-mediated abrogation of Rap1 overexpression increased the viability of these cells, suggesting that Rap1 is also an endogenous regulator of Ras-MAP kinase signaling in melanomas.
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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.