ArticleCancers2019
Amino Acid Deprivation-Induced Autophagy Requires Upregulation of DIRAS3 through Reduction of E2F1 and E2F4 Transcriptional Repression.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Autophagy in Ovarian Cancer, an Opportunity or an Additional Threat?International journal of molecular sciences · 2026Review
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy.Discover oncology · 2024Review
- Cellular Dormancy in Cancer: Mechanisms and Potential Targeting Strategies.Cancer research and treatment · 2023Review
- E2F4DN Transgenic Mice: A Tool for the Evaluation of E2F4 as a Therapeutic Target in Neuropathology and Brain Aging.International journal of molecular sciences · 2022Review
- Prognostic Model and Nomogram Construction and Validation With an Autophagy-Related Gene Signature in Low-Grade Gliomas.Frontiers in genetics · 2022Article
- Review
- MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination.Journal of cellular and molecular medicine · 2021Article
- Review
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Article
- How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer.Frontiers in oncology · 2020Review
- Amino Acid Starvation Sensitizes Resistant Breast Cancer to Doxorubicin-Induced Cell Death.Frontiers in cell and developmental biology · 2020Article
- DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1.Cancers · 2019Article
- Autophagy and LRRK2 in the Aging Brain.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Failure to cure ovarian cancer relates to the persistence of dormant, drug-resistant cancer cells following surgery and chemotherapy. "Second look" surgery can detect small, poorly vascularized nodules of persistent ovarian cancer in ~50% of patients, where >80% are undergoing autophagy and express DIRAS3. Autophagy is one mechanism by which dormant cancer cells survive in nutrient poor environments. DIRAS3 is a tumor suppressor gene downregulated in >60% of primary ovarian cancers by genetic, epigenetic, transcriptional and post-transcriptional mechanisms, that upon re-expression can induce autophagy and dormancy in a xenograft model of ovarian cancer. We examined the expression of DIRAS3 and autophagy in ovarian cancer cells following nutrient deprivation and the mechanism by which they are upregulated. We have found that DIRAS3 mediates autophagy induced by amino acid starvation, where nutrient sensing by mTOR plays a central role. Withdrawal of amino acids downregulates mTOR, decreases binding of E2F1/4 to the DIRAS3 promoter, upregulates DIRAS3 and induces autophagy. By contrast, acute amino acid deprivation did not affect epigenetic regulation of DIRAS3 or expression of miRNAs that regulate DIRAS3. Under nutrient poor conditions DIRAS3 can be transcriptionally upregulated, inducing autophagy that could sustain dormant ovarian cancer 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.