ArticleOncotarget2017
Extracellular signal-regulated kinase 8-mediated NF-κB activation increases sensitivity of human lung cancer cells to arsenic trioxide.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- MAPK15 PreventsInternational journal of molecular sciences · 2025Article
- Atypical MAPKs in cancer.The FEBS journal · 2025Review
- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer.International journal of molecular sciences · 2023Article
- Atypical MAP kinases - new insights and directions from amoeba.Journal of cell science · 2023Review
- Article
- Transcriptional upregulation of MAPK15 by NF-κB signaling boosts the efficacy of combination therapy with cisplatin and TNF-α.iScience · 2022Article
- Interleukin-38 ameliorates poly(I:C) induced lung inflammation: therapeutic implications in respiratory viral infections.Cell death & disease · 2021Article
- Enhanced expression of queuine tRNA-ribosyltransferase 1 (Annals of translational medicine · 2020Article
- IGF1R and MAPK15 Emerge as Potential Targets of Pentabromobenzylisothioureas in Lung Neuroendocrine Neoplasms.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Metastasis-associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c-Jun/MMPs pathway.Oncology letters · 2020Article
- A candidate for lung cancer treatment: arsenic trioxide.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Quantitative Proteomic Analysis Identifies MAPK15 as a Potential Regulator of Radioresistance in Nasopharyngeal Carcinoma Cells.Frontiers in oncology · 2018Article
- Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I.Cell death & disease · 2017Article
- Article
- Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells.Cell cycle (Georgetown, Tex.) · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular signal-regulated kinase 8 (ERK8), also known as mitogen-activated protein kinase 15 (MAPK15), is the most recently identified protein kinase of the ERK family members and yet the least has been studied so far. Here, we report that ERK8 is highly expressed in several human lung cancer cell lines and is positively correlated with their sensitivities to the anti-cancer drug arsenic trioxide (As2O3). As2O3 at physiologically relevant concentrations (5-20 μM) potently stimulates the phosphorylation of ERK8 at Thr175 and Tyr177 within the TEY motif in the kinase domain, leading to its activation. Interestingly, activated ERK8 interacts and directly phosphorylates IkappaBalpha (IκBα) at Ser32 and Ser36, resulting in IκBα degradation. This in turn promotes nuclear factor-kappaB (NF-κB) p65 nuclear translocation and chromatin-binding, as well as the subsequent induction and activation of proteins involved in apoptosis. We also show that stable short-hairpin RNA-specific knockdown of endogenous ERK8 or inhibition of NF-κB activity by NF-κB inhibitor in high ERK8 expressing lung cancer H1299 cells blunted the As2O3-induced NF-κB activation and cytotoxicity towards these cells, indicating the critical role of ERK8 and NF-κB in mediating the As2O3 effects. Taken together, our findings suggest for the first time a regulatory paradigm of NF-κB activation by ERK8 upon As2O3 treatment in human lung cancer cells; and implicate a potential therapeutic advantage of As2O3 that might gain more selective killing of cancer cells with high ERK8 expression.
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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.