ArticleGenes & cancer2014
DEPTOR is linked to a TORC1-p21 survival proliferation pathway in multiple myeloma cells.
Article in Genes & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells.The Journal of clinical investigation · 2023Article
- Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products.International journal of molecular sciences · 2023Review
- An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma.Cell death & disease · 2022Article
- Review
- [MicroRNA-671-3p suppresses proliferation and invasion of breast cancer cells by targeting DEPTOR].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- RETRACTED: A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor Cytotoxicity.Molecular cancer therapeutics · 2019Article
- HMGB1 knockdown increases MM cell vulnerability by regulating autophagy and DNA damage repair.Journal of experimental & clinical cancer research : CR · 2018Article
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- Deptor Is a Novel Target of Wnt/β-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth.Cancer research · 2018Article
- Deptor: not only a mTOR inhibitor.Journal of experimental & clinical cancer research : CR · 2017Review
- RETRACTED: Cytotoxic Properties of a DEPTOR-mTOR Inhibitor in Multiple Myeloma Cells.Cancer research · 2016Article
- DEPTOR suppresses the progression of esophageal squamous cell carcinoma and predicts poor prognosis.Oncotarget · 2016Article
- High DEPTOR expression correlates with poor prognosis in patients with esophageal squamous cell carcinoma.OncoTargets and therapy · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We investigated the mechanism by which gene silencing of the mTOR inhibitor, DEPTOR, induces cytoreductive effects on multiple myeloma (MM) cells. DEPTOR knockdown resulted in anti-MM effects in several MM cell lines. Using an inducible shRNA to silence DEPTOR, 8226 MM cells underwent TORC1 activation, downregulation of AKT/SGK activity, apoptosis, cell cycle arrest and senescence. These latter cytotoxic effects were prevented by TORC1 paralysis (Raptor knockdown) but not by over-expression of AKT activity. In addition, DEPTOR knockdown-induced MM death was not associated with activation of the unfolded protein response, suggesting that enhanced ER stress did not play a role. In contrast, DEPTOR knockdown in 8226 cells induced p21 expression, independent of p53, and p21 knockdown prevented all of the cytotoxic effects following DEPTOR silencing. DEPTOR silencing resulted in p21 upregulation in additional MM cell lines. Furthermore, DEPTOR silencing in a murine xenograft model resulted in anti-MM effects associated with p21 upregulation. DEPTOR knockdown also resulted in a decreased expression of p21-targeting miRNAs and transfection of miRNA mimics prevented p21 upregulation and apoptosis following DEPTOR silencing. Use of a shRNA-resistant DEPTOR construct ruled out off-target effects of the shRNA. These results indicate that DEPTOR regulates growth and survival of MM cells via a TORC1/p21 pathway and suggest an involvement of p21-targeted miRNAs.
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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.