ArticleOncotarget2015
GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 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
14 citing papers in PubMed, 20 citations in OpenAlex.
- Rapamycin Prevents Sulfate-Reducing Bacteria-Induced Effects on Snail and GSK-3 and Impaired Intestinal Barrier.Microorganisms · 2026Article
- Multi-omics analysis identifies TLRscore for prognostic prediction and highlights TLR8 in macrophage-mediated antitumor immunity of lung adenocarcinoma.Frontiers in immunology · 2026Article
- Biphasic control of the B cell transcriptome by mTORC1 and GSK3.Cell reports · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?Frontiers of medicine · 2021Review
- Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.BMC cancer · 2021Article
- Regulation of GSK3 cellular location by FRAT modulates mTORC1-dependent cell growth and sensitivity to rapamycin.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
- Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models.Scientific reports · 2019Article
- A molecular cascade modulates MAP1B and confers resistance to mTOR inhibition in human glioblastoma.Neuro-oncology · 2018Article
- HDAC inhibition as a treatment concept to combat temsirolimus-resistant bladder cancer cells.Oncotarget · 2017Article
- The Enigma of Rapamycin Dosage.Molecular cancer therapeutics · 2016Review
- Article
- The anti-tumor NC1 domain of collagen XIX inhibits the FAK/ PI3K/Akt/mTOR signaling pathway through αvβ3 integrin interaction.Oncotarget · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The single-agent activity of rapalogs (rapamycin and its analogues) in most tumor types has been modest at best. The underlying mechanisms are largely unclear. In this report, we have uncovered a critical role of GSK3 in regulating degradation of some oncogenic proteins induced by rapalogs and cell sensitivity to rapalogs. The basal level of GSK3 activity was positively correlated with cell sensitivity of lung cancer cell lines to rapalogs. GSK3 inhibition antagonized rapamycin's growth inhibitory effects both in vitro and in vivo, while enforced activation of GSK3β sensitized cells to rapamycin. GSK3 inhibition rescued rapamcyin-induced reduction of several oncogenic proteins such as cyclin D1, Mcl-1 and c-Myc, without interfering with the ability of rapamycin to suppress mTORC1 signaling and cap binding. Interestingly, rapamycin induces proteasomal degradation of these oncogenic proteins, as evidenced by their decreased stabilities induced by rapamcyin and rescue of their reduction by proteasomal inhibition. Moreover, acute or short-time rapamycin treatment dissociated not only raptor, but also rictor from mTOR in several tested cell lines, suggesting inhibition of both mTORC1 and mTORC2. Thus, induction of GSK3-dependent degradation of these oncogenic proteins is likely secondary to mTORC2 inhibition; this effect should be critical for rapamycin to exert its anticancer activity.
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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.