ArticleJournal of molecular medicine (Berlin, Germany)2012
The mitogen-activated protein kinase (MAPK) cascade controls phosphatase and tensin homolog (PTEN) expression through multiple mechanisms.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Synthetic lethal approaches to target cancers with loss of PTEN function.Genes & diseases · 2023Article
- PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.OncoTargets and therapy · 2022Article
- Regulation of autophagy as a therapeutic option in glioblastoma.Apoptosis : an international journal on programmed cell death · 2021Review
- MiRNA-202-5p promotes Colorectal Carcinogenesis through suppression of PTEN.Journal of Cancer · 2021Article
- Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor.Frontiers in physiology · 2021Review
- Blocking Y-Box Binding Protein-1 through Simultaneous Targeting of PI3K and MAPK in Triple Negative Breast Cancers.Cancers · 2020Article
- Role of Ubiquitination in PTEN Cellular Homeostasis and Its Implications in GB Drug Resistance.Frontiers in oncology · 2020Review
- PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition.Cancers · 2019Review
- C-Jun drives melanoma progression in PTEN wild type melanoma cells.Cell death & disease · 2019Article
- PTEN Tumor-Suppressor: The Dam of Stemness in Cancer.Cancers · 2019Review
- Review
- Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System.Molecular therapy. Nucleic acids · 2019Article
- Article
- The functions and regulation of the PTEN tumour suppressor: new modes and prospects.Nature reviews. Molecular cell biology · 2018Review
- Therapeutic potential of combined BRAF/MEK blockade in BRAF-wild type preclinical tumor models.Journal of experimental & clinical cancer research : CR · 2018Article
- Enhancer of zeste homolog 2-catalysed H3K27 trimethylation plays a key role in acute-on-chronic liver failure via TNF-mediated pathway.Cell death & disease · 2018Article
- Review
- PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer.Scientific reports · 2017Article
- Reconstruction of Alar Nasal Cartilage Defects Using a Tissue Engineering Technique Based on a Combined Use of Autologous Chondrocyte Micrografts and Platelet-rich Plasma: Preliminary Clinical and Instrumental Evaluation.Plastic and reconstructive surgery. Global open · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitogen-activated protein kinase (MAPK) and PI3K pathways are regulated by extensive crosstalk, occurring at different levels. In tumors, transactivation of the alternate pathway is a frequent "escape" mechanism, suggesting that combined inhibition of both pathways may achieve synergistic antitumor activity. Here we show that, in the M14 melanoma model, simultaneous inhibition of both MEK and mammalian target of rapamycin (mTOR) achieves synergistic effects at suboptimal concentrations, but becomes frankly antagonistic in the presence of relatively high concentrations of MEK inhibitors. This observation led to the identification of a novel crosstalk mechanism, by which either pharmacologic or genetic inhibition of constitutive MEK signaling restores phosphatase and tensin homolog (PTEN) expression, both in vitro and in vivo, and inhibits downstream signaling through AKT and mTOR, thus bypassing the need for double pathway blockade. This appears to be a general regulatory mechanism and is mediated by multiple mechanisms, such as MAPK-dependent c-Jun and miR-25 regulation. Finally, PTEN upregulation appears to be a major effector of MEK inhibitors' antitumor activity, as cancer cells in which PTEN is inactivated are consistently more resistant to the growth inhibitory and anti-angiogenic effects of MEK blockade.
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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.