ArticleOncotarget2014
The MAPK pathway as an apoptosis enhancer in melanoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Regulation and Implementation of Apoptosis in Melanoma Tumor Cells withCurrent issues in molecular biology · 2026Review
- Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.Cancers · 2024Article
- NRF2 Enables EGFR Signaling in Melanoma Cells.International journal of molecular sciences · 2021Article
- Progress in experimental research on SPRED protein family.The Journal of international medical research · 2020Review
- Effective Treatment of Metastatic Melanoma by Combining MAPK and PI3K Signaling Pathway Inhibitors.International journal of molecular sciences · 2019Article
- A hypergraph-based method for large-scale dynamic correlation study at the transcriptomic scale.BMC genomics · 2019Article
- The Sprouty/Spred family as tumor suppressors: Coming of age.Cancer science · 2019Review
- BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1.Oncogenesis · 2018Article
- The varied distribution and impact of RAS codon and other key DNA alterations across the translocation cyclin D subgroups in multiple myeloma.Oncotarget · 2017Article
- Synergistic combination of DT-13 and topotecan inhibits human gastric cancer via myosin IIA-induced endocytosis of EGF receptor in vitro and in vivo.Oncotarget · 2016Article
- Tumor suppressor Spred2 interaction with LC3 promotes autophagosome maturation and induces autophagy-dependent cell death.Oncotarget · 2016Article
- PP2B and ERK1/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines.International journal of oncology · 2016Article
- Article
- Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen-Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma.Neurochemical research · 2015Article
- Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAF(V600E)-mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAF(V600E)-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
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.