ArticleMolecular cancer therapeutics2011
RETRACTED: Inhibition of SAPK2/p38 enhances sensitivity to mTORC1 inhibition by blocking IRES-mediated translation initiation in glioblastoma.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Regulation of cagA-Helicobacter on gastric PIM2 expression in gastric cancer.Cancer biomarkers : section A of Disease markers · 2024Article
- Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.Brain sciences · 2023Review
- Retraction: Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma.PloS one · 2023Article
- Critical Role for Cap-Independent c-MYC Translation in Progression of Multiple Myeloma.Molecular cancer therapeutics · 2022Article
- Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance.Journal of cancer research and clinical oncology · 2022Review
- Repurposing Potential of Riluzole as an ITAF Inhibitor in mTOR Therapy Resistant Glioblastoma.International journal of molecular sciences · 2020Article
- Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential.Cells · 2019Review
- mTORC2/AKT/HSF1/HuR constitute a feed-forward loop regulating Rictor expression and tumor growth in glioblastoma.Oncogene · 2018Article
- Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma.PloS one · 2017Article
- Mechanistic Target of Rapamycin (mTOR) Inhibition Synergizes with Reduced Internal Ribosome Entry Site (IRES)-mediated Translation of Cyclin D1 and c-MYC mRNAs to Treat Glioblastoma.The Journal of biological chemistry · 2016Article
- Mechanisms of protein synthesis activation following exercise: new pieces to the increasingly complex puzzle.The Journal of physiology · 2015Article
- Phosphorylation of the Hippo Pathway Component AMOTL2 by the mTORC2 Kinase Promotes YAP Signaling, Resulting in Enhanced Glioblastoma Growth and Invasiveness.The Journal of biological chemistry · 2015Article
- Article
- mTORC2 modulates feedback regulation of p38 MAPK activity via DUSP10/MKP5 to confer differential responses to PP242 in glioblastoma.Genes & cancer · 2014Article
- Lifespan extension in a semelparous chordate occurs via developmental growth arrest just prior to meiotic entry.PloS one · 2014Article
- RNA-binding proteins impacting on internal initiation of translation.International journal of molecular sciences · 2013Review
- NPV-LDE-225 (Erismodegib) inhibits epithelial mesenchymal transition and self-renewal of glioblastoma initiating cells by regulating miR-21, miR-128, and miR-200.Neuro-oncology · 2013Article
- IRES-dependent translation of egr2 is induced under inflammatory conditions.RNA (New York, N.Y.) · 2012Article
Corrections and comments
- Retracted
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
A variety of mechanisms confer hypersensitivity of tumor cells to the macrolide rapamycin, the prototypic mTORC1 inhibitor. Several studies have shown that the status of the AKT kinase plays a critical role in determining hypersensitivity. Cancer cells in which AKT activity is elevated are exquisitely sensitive to mTORC1 inhibitors while cells in which the kinase is quiescent are relatively resistant. Our previous work has shown that a transcript-specific protein synthesis salvage pathway is operative in cells with quiescent AKT levels, maintaining the translation of crucial mRNAs involved in cell-cycle progression in the face of global eIF-4E-mediated translation inhibition. The activation of this salvage pathway is dependent on SAPK2/p38-mediated activation of IRES-dependent initiation of the cyclin D1 and c-MYC mRNAs, resulting in the maintenance of their protein expression levels. Here, we show that both genetic and pharmacologic inhibition of SAPK2/p38 in glioblastoma multiforme cells significantly reduces rapamycin-induced IRES-mediated translation initiation of cyclin D1 and c-MYC, resulting in increased G(1) arrest in vitro and inhibition of tumor growth in xenografts. Moreover, we observed that the AKT-dependent signaling alterations seen in vitro are also displayed in engrafted tumors cells and were able to show that combined inhibitor treatments markedly reduced the mRNA translational state of cyclin D1 and c-MYC transcripts in tumors isolated from mice. These data support the combined use of SAPK2/p38 and mTORC1 inhibitors to achieve a synergistic antitumor therapeutic response, particularly in rapamycin-resistant quiescent AKT-containing cells.
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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.