ArticlePloS one2013
Ras and Rac1, frequently mutated in melanomas, are activated by superoxide anion, modulate Dnmt1 level and are causally related to melanocyte malignant transformation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
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- Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression.International journal of molecular sciences · 2022Article
- Inhibiting Histone and DNA Methylation Improves Cancer Vaccination in an Experimental Model of Melanoma.Frontiers in immunology · 2022Article
- Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.International journal of molecular sciences · 2021Article
- Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression.Neoplasia (New York, N.Y.) · 2021Article
- Exploration of the Immune-Related Signatures and Immune Infiltration Analysis in Melanoma.Analytical cellular pathology (Amsterdam) · 2021Article
- PTPN11 mutation with additional somatic alteration indicates unfavorable outcome in juvenile myelomonocytic leukemia: a retrospective clinical study from a single center.European journal of pediatrics · 2020Article
- Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival.International journal of cancer · 2018Article
- Abnormal Epigenetic Regulation of Immune System during Aging.Frontiers in immunology · 2018Review
- SIRT1 regulates Mxd1 during malignant melanoma progression.Oncotarget · 2017Article
- RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia.Nature communications · 2017Article
- Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities.Clinical epigenetics · 2017Review
- Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans.Free radical biology & medicine · 2016Article
- Mechanisms of superoxide signaling in epigenetic processes: relation to aging and cancer.Aging and disease · 2015Review
- Cellular Mechanisms of Oxidative Stress and Action in Melanoma.Oxidative medicine and cellular longevity · 2015Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A melanocyte malignant transformation model was developed in our laboratory, in which different melanoma cell lines were obtained after submitting the non-tumorigenic melanocyte lineage melan-a to sequential cycles of anchorage impediment. Our group has already showed that increased superoxide level leads to global DNA hypermemethylation as well increased Dnmt1 expression few hours after melanocyte anchorage blockade. Here, we showed that Ras/Rac1/ERK signaling pathway is activated in melanocytes submitted to anchorage impediment, regulating superoxide levels, global DNA methylation, and Dnmt1 expression. Interestingly, Ras and Rac1 activation is not related to codon mutations, but instead regulated by superoxide. Moreover, the malignant transformation was drastically compromised when melan-a melanocytes were submitted to sequential cycles of anchorage blockage in the presence of a superoxide scavenger. This aberrant signaling pathway associated with a sustained stressful condition, which might be similar to conditions such as UV radiation and inflammation, seems to be an early step in malignant transformation and to contribute to an epigenetic reprogramming and the melanoma development.
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