ArticleAutophagy2024
DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Restoring glucose metabolic homeostasis to attenuate ovarian aging: mechanisms and clinical prospects.Journal of ovarian research · 2026Review
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- Photodynamic activation of a KRAS RNA G-quadruplex-targeted photosensitizer induces ferroptosis in cisplatin-resistant non-small cell lung cancer.The Journal of biological chemistry · 2026Article
- LKB1 promotes lung adenocarcinoma cell senescence by suppressing the O-GlcNAc glycosylation-mediated activation of telomerase.Frontiers in pharmacology · 2026Article
- Autophagy modulation in gynaecologic oncology: insights into immune regulation and therapeutic potential.Frontiers in immunology · 2026Review
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- Article
- Transcriptional patterns of cancer-related genes in primary and metastatic tumours revealed by machine learning.BMC biology · 2025Article
- BST2 and DIRAS3 Drive Immune Evasion and Tumor Progression in High-Grade Glioma.International journal of molecular sciences · 2025Article
- Dual functional nanoplatforms potentiate osteosarcoma immunotherapy via microenvironment modulation.National science review · 2025Article
- Reduction reactions dominate the interactions between Mg alloys and cells: Understanding the mechanisms.Bioactive materials · 2025Article
- The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal CDKN1B/p27 localization, and inducing autophagic gene expression. Treatment with chloroquine or the novel dimeric chloroquine analog DC661 significantly enhances DIRAS3-mediated inhibition of mutant KRAS tumor cell growth in vitro and in vivo. Taken together, our study demonstrates that DIRAS3 plays a critical role in regulating mutant KRAS-driven oncogenesis in PDAC and LGSOC.
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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.