ArticleMolecular oncology2016
Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors.
Article in Molecular oncology, 2016. 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 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Nelfinavir triggers ferroptosis by inducing ER stress mediated downregulation of GPX4/GSH system, upregulation of NRF2/HO-1 axis, and mitochondrial impairment in hepatocellular carcinoma cells.Cell death discovery · 2025Article
- Endoplasmic reticulum stress response pathway-mediated cell death in ovarian cancer.Frontiers in oncology · 2024Review
- Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells.Cancers · 2023Article
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- Enzymatic synthesis of new antimicrobial peptides for food purposes.Frontiers in microbiology · 2023Article
- mPR-Specific Actions Influence Maintenance of the Blood-Brain Barrier (BBB).International journal of molecular sciences · 2022Article
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- Anticancer effects of mifepristone on human uveal melanoma cells.Cancer cell international · 2021Article
- The gold complex auranofin: new perspectives for cancer therapy.Discover oncology · 2021Review
- Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer.Frontiers in cell and developmental biology · 2021Article
- Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response.International journal of molecular sciences · 2019Review
- Advanced assessment of migration and invasion of cancer cells in response to mifepristone therapy using double fluorescence cytochemical labeling.BMC cancer · 2019Article
- Application of a New Multiplexed Array for Rapid, Sensitive, Simultaneous and Quantitative Assessment of Spliced and Unspliced XBP1.Biological procedures online · 2019Article
- Highly Dynamic Changes in the Activity and Regulation of Macroautophagy in Hearts Subjected to Increased Proteotoxic Stress.Frontiers in physiology · 2019Article
- Mifepristone inhibits non-small cell lung carcinoma cellular escape from DNA damaging cisplatin.Cancer cell international · 2018Article
- Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production.Frontiers in immunology · 2017Article
- Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors.Molecular oncology · 2016Article
- Transcriptomic Profiling of MDA-MB-231 Cells Exposed toCancer genomics & proteomicsReview
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). GRP78 and CHOP were upregulated by mifepristone in ovarian cancer cells regardless of p53 status and platinum sensitivity. Further studies revealed that the three UPR-associated pathways, PERK, IRE1α, and ATF6, were activated by mifepristone. Also, the synthetic steroid acutely increased mRNA translation rate, which, if prevented, abrogated the splicing of XBP1 mRNA, a non-translatable readout of IRE1α activation. Moreover, mifepristone increased LC3-II levels due to increased autophagic flux. When the autophagic-lysosomal pathway was inhibited with chloroquine, mifepristone was lethal to the cells. Lastly, doses of proteasome inhibitors that are inadequate to block the activity of the proteasomes, caused cell death when combined with mifepristone; this phenotype was accompanied by accumulation of poly-ubiquitinated proteins denoting proteasome inhibition. The stimulation by mifepristone of ER stress and autophagic flux offers a therapeutic opportunity for utilizing this compound to sensitize ovarian cancer cells to proteasome or lysosome inhibitors.
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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.