ArticleEMBO reports2023
Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Article
- Mfn1-mediated imbalanced mitochondrial dynamics promotes ovarian cancer stemness by inducing metabolic reprogramming.Journal of physiology and biochemistry · 2026Article
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- Cancer Stem Cells Shift Metabolite Acetyl-Coenzyme A to Abrogate the Differentiation of CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Cancer stem cell programs S-nitrosylation and deubiquitination of FoxP3 protein to promote regulatory T cell differentiation.Frontiers in immunology · 2026Article
- A Pyrimidine-Based Tubulin Inhibitor Shows Potent Anti-Glioblastoma Activity In Vitro and In Vivo.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- BNIP3L/BNIP3-Mediated Mitophagy Contributes to the Maintenance of Ovarian Cancer Stem Cells.Journal of cellular and molecular medicine · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Single-cell multi-omics elucidates the role of RPS27-RPS24 fusion gene in osteosarcoma chemoresistance and metabolic regulation.Cell death discovery · 2025Article
- Role of toll-like receptors in pulmonary immunity: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- Mitophagy in the mechanisms of treatment resistance in solid tumors.Oncology reviews · 2025Review
- Evaluation of Mitochondrial Phagy (Mitophagy) in Human Non-small Adenocarcinoma Tumor Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Fuel for thought: targeting metabolism in lung cancer.Translational lung cancer research · 2024Review
- Nitric oxide facilitates the S-nitrosylation and deubiquitination of Notch1 protein to maintain cancer stem cells in human NSCLC.Journal of cellular and molecular medicine · 2024Article
- The mitochondrial stress signaling tunes immunity from a view of systemic tumor microenvironment and ecosystem.iScience · 2024Review
- Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine.The EPMA journal · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While previous studies have identified cancer stem-like cells (CSCs) as a crucial driver for chemoresistance and tumor recurrence, the underlying mechanisms for populating the CSC pool remain unclear. Here, we identify hypermitophagy as a feature of human lung CSCs, promoting metabolic adaption via the Notch1-AMPK axis to drive CSC expansion. Specifically, mitophagy is highly active in CSCs, resulting in increased mitochondrial DNA (mtDNA) content in the lysosome. Lysosomal mtDNA acts as an endogenous ligand for Toll-like receptor 9 (TLR9) that promotes Notch1 activity. Notch1 interacts with AMPK to drive lysosomal AMPK activation by inducing metabolic stress and LKB1 phosphorylation. This TLR9-Notch1-AMPK axis supports mitochondrial metabolism to fuel CSC expansion. In patient-derived xenograft chimeras, targeting mitophagy and TLR9-dependent Notch1-AMPK pathway restricts tumor growth and CSC expansion. Taken together, mitochondrial hemostasis is interlinked with innate immune sensing and Notch1-AMPK activity to increase the CSC pool of human lung cancer.
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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.