ArticleAutophagy2018
RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 57 citations in OpenAlex.
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Nutrient stress diverts RRN3 from rRNA transcription to alternative polyadenylation of autophagy mRNAs in ovarian cancer.Cell death & disease · 2025Article
- DIRAS1 Drives Oxaliplatin Resistance in Colorectal Cancer via PHB1-Mediated Mitochondrial Homeostasis.Biology · 2025Article
- eNAMPT/Ac-STAT3/DIRAS2 Axis Promotes Development and Cancer Stemness in Triple-Negative Breast Cancer by Enhancing Cytokine Crosstalk Between Tumor-Associated Macrophages and Cancer Cells.International journal of biological sciences · 2025Article
- M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells.Cancer biology & therapy · 2024Article
- The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.International journal of molecular sciences · 2024Review
- Review
- Ferroptosis, autophagy, tumor and immunity.Heliyon · 2023Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention.International journal of molecular sciences · 2022Review
- Germline stem cells in human.Signal transduction and targeted therapy · 2022Review
- Multi-Omics-Based Autophagy-Related Untypical Subtypes in Patients with Cerebral Amyloid Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Regulation of GTPase function by autophosphorylation.Molecular cell · 2022Article
- DIRAS2 Is a Prognostic Biomarker and Linked With Immune Infiltrates in Melanoma.Frontiers in oncology · 2022Article
- Comprehensive analysis of tissue proteomics in patients with papillary thyroid microcarcinoma uncovers the underlying mechanism of lymph node metastasis and its significant sex disparities.Frontiers in oncology · 2022Article
- Diverse Ras-related GTPase DIRAS2, downregulated by PSMD2 in a proteasome-mediated way, inhibits colorectal cancer proliferation by blocking NF-κB signaling.International journal of biological sciences · 2022Article
- Oxidative damage-induced hyperactive ribosome biogenesis participates in tumorigenesis of offspring by cross-interacting with the Wnt and TGF-β1 pathways in IVF embryos.Experimental & molecular medicine · 2021Article
- Frequent Epigenetic Inactivation of DIRAS-1 and DIRAS-2 Contributes to Chemo-Resistance in Gliomas.Cancers · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Among the 3 GTPases in the DIRAS family, DIRAS3/ARHI is the best characterized. DIRAS3 is an imprinted tumor suppressor gene that encodes a 26-kDa GTPase that shares 60% homology to RAS and RAP. DIRAS3 is downregulated in many tumor types, including ovarian cancer, where re-expression inhibits cancer cell growth, reduces motility, promotes tumor dormancy and induces macroautophagy/autophagy. Previously, we demonstrated that DIRAS3 is required for autophagy in human cells. Diras3 has been lost from the mouse genome during evolutionary re-arrangement, but murine cells can still undergo autophagy. We have tested whether DIRAS1 and DIRAS2, which are homologs found in both human and murine cells, could serve as surrogates to DIRAS3 in the murine genome affecting autophagy and cancer cell growth. Similar to DIRAS3, these 2 GTPases share 40-50% homology to RAS and RAP, but differ from DIRAS3 primarily in the lengths of their N-terminal extensions. We found that DIRAS1 and DIRAS2 are downregulated in ovarian cancer and are associated with decreased disease-free and overall survival. Re-expression of these genes suppressed growth of human and murine ovarian cancer cells by inducing autophagy-mediated cell death. Mechanistically, DIRAS1 and DIRAS2 induce and regulate autophagy by inhibition of the AKT1-MTOR and RAS-MAPK signaling pathways and modulating nuclear localization of the autophagy-related transcription factors FOXO3/FOXO3A and TFEB. Taken together, these data suggest that DIRAS1 and DIRAS2 likely serve as surrogates in the murine genome for DIRAS3, and may function as a backup system to fine-tune autophagy in humans.
Indexed as
Identifiers
What OpenQuestion holds
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.