ArticleCell cycle (Georgetown, Tex.)2012
Regulating the response to targeted MEK inhibition in melanoma: enhancing apoptosis in NRAS- and BRAF-mutant melanoma cells with Wnt/β-catenin activation.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Ras-MAPK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis.Cell communication and signaling : CCS · 2026Article
- Nischarin expression may have differing roles in male and female melanoma patients.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Inhibition of Axl Promotes the Therapeutic Effect of Targeted Inhibition of the PI3K/Akt Pathway in NRAS Mutant Melanoma Cells.Journal of oncology · 2022Article
- Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A Framework of Major Tumor-Promoting Signal Transduction Pathways Implicated in Melanoma-Fibroblast Dialogue.Cancers · 2020Review
- Long-Term Inhibition of Notch in A-375 Melanoma Cells Enhances Tumor Growth Through the Enhancement ofFrontiers in oncology · 2020Article
- Article
- Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial-mesenchymal transition by targetting PMEL through the Wnt signaling pathway.Bioscience reports · 2017Article
- Wnt signaling in triple-negative breast cancer.Oncogenesis · 2017Review
- Searching for the Chokehold of NRAS Mutant Melanoma.The Journal of investigative dermatology · 2016Review
- A Nexus Consisting of Beta-Catenin and Stat3 Attenuates BRAF Inhibitor Efficacy and Mediates Acquired Resistance to Vemurafenib.EBioMedicine · 2016Article
- Treatment of NRAS-mutant melanoma.Current treatment options in oncology · 2015Review
- SMK-17, a MEK1/2-specific inhibitor, selectively induces apoptosis in β-catenin-mutated tumors.Scientific reports · 2015Article
- Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives.World journal of orthopedics · 2014Review
- Molecular pathways: targeting NRAS in melanoma and acute myelogenous leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
- Evaluating melanoma drug response and therapeutic escape with quantitative proteomics.Molecular & cellular proteomics : MCP · 2014Article
- GSK-3 as potential target for therapeutic intervention in cancer.Oncotarget · 2014Review
- Pathways and therapeutic targets in melanoma.Oncotarget · 2014Review
- α-catenin. A tumor suppressor beyond adherens junctions.Cell cycle (Georgetown, Tex.) · 2014Article
- Profile of selumetinib and its potential in the treatment of melanoma.OncoTargets and therapy · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The limitations of revolutionary new mutation-specific inhibitors of BRAF(V600E) include the universal recurrence seen in melanoma patients treated with this novel class of drugs. Recently, our lab showed that simultaneous activation of the Wnt/β-catenin signaling pathway and targeted inhibition of BRAF(V600E) by PLX4720 synergistically induces apoptosis across a spectrum of BRAF(V600E) melanoma cell lines. As a follow-up to that study, treatment of BRAF-mutant and NRAS-mutant melanoma lines with WNT3A and the MEK inhibitor AZD6244 also induces apoptosis. The susceptibility of BRAF-mutant lines and NRAS-mutant lines to apoptosis correlates with negative regulation of Wnt/β-catenin signaling by ERK/MAPK signaling and dynamic decreases in abundance of the downstream scaffolding protein, AXIN1. Apoptosis-resistant NRAS-mutant lines can sensitize to AZD6244 by pretreatment with AXIN1 siRNA, similar to what we previously reported in BRAF-mutant cell lines. Taken together, these findings indicate that NRAS-mutant melanoma share with BRAF-mutant melanoma the potential to regulate apoptosis upon MEK inhibition through WNT3A and dynamic regulation of cellular AXIN1. Understanding the cellular context that makes melanoma cells susceptible to this combination treatment will contribute to the study and development of novel therapeutic combinations that may lead to more durable responses.
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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.