ArticleNature communications2020
ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 135 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- ISGylation-mediated stabilization of CYP4Z1 fuels breast cancer initiation and progression.Experimental & molecular medicine · 2026Article
- Semaglutide targets the Isg15-FUNDC1 axis: suppressing IFN-β overactivation and attenuating blood-brain barrier injury in diabetic intracerebral hemorrhage.Journal of neuroinflammation · 2026Article
- Capsaicin Receptor TRPV1 Delays Aortic Aging in Atherosclerotic Mice by Inhibiting the ISG15-p53 Pathway.Journal of cellular and molecular medicine · 2026Article
- Human microglia express anti-inflammatory ISG15 in response to Neisseria meningitidis.Neuroscience letters · 2026Article
- Proteomics and tracer metabolomics link GAPDH ISGylation to glycolytic control.Genome biology · 2026Article
- Mitophagy in pancreatic cancer: mechanistic insights and implications for novel therapeutic strategies.Cell death discovery · 2026Review
- ISG15-driven immune modulation and tumor progression in breast cancer metastasis: insights from single-cell and spatial transcriptomics.BMC medicine · 2026Article
- Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity.Viruses · 2026Review
- Hyaluronic Acid-Palmitate Nanoparticle Delivery of Carbonic Anhydrase Inhibitors Impairs Growth and Early Metabolism inInternational journal of molecular sciences · 2026Article
- Single-cell RNA sequencing reveals immune regulatory mechanisms and molecular therapeutic strategies in the microenvironment of multiple myeloma.International journal of surgery (London, England) · 2026Article
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Systemic inflammatory and metabolic disease progression persists despite prevention of myocarditis inFrontiers in immunology · 2026Article
- The simultaneous targeted Inhibition of ISG15 and HMGCR disrupts cancer stemness through metabolic collapse and induces synthetic lethality in pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma.Cell death and differentiation · 2025Article
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- SLC7A11-AS1 contributes to prolonged activation of activin A/Smad signaling by suppressing PPM1A myristoylation in pancreatic cancer.British journal of cancer · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness.
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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.