ArticleJournal of extracellular vesicles2021
Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion.
Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 121 citations in OpenAlex.
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Cancer-Associated Fibroblasts Promote Glucose Metabolic Reprogramming and Progression of Triple-Negative Breast Cancer via Exosomal circFAD104-Mediated Intercellular Communication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CD147 promotes NSCLC metastasis by inducing secretory autophagy-dependent exosome secretion via TRIM56-mediated ubiquitination and degradation of GCN2.Cell death and differentiation · 2026Article
- Modulation of tumor-derived exosomes and reprogramming of cancer-associated fibroblasts for colorectal cancer therapy.Molecular cancer · 2026Article
- VAMP4/STX8 Mediate the Autophagic Secretion of Mitochondria and Promote TAMs Polarization in HNSCC.Journal of extracellular vesicles · 2026Article
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- BMI and Breast Subcutaneous Fat: Potential Indicators for Ultrasound Diagnosis of Breast Cancer?Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine · 2026Article
- Review
- Targeting hypoxic exosomal IGFBP2 overcomes CD47-mediated immune evasion in glioblastoma.Cell death & disease · 2026Article
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Extracellular vesicles as nanocarriers in glioblastoma: implications for chemoresistance and immune evasion.Frontiers in molecular neuroscience · 2026Review
- Cancer-associated fibroblast-derived extracellular vesicles regulate lipophagy through PLIN2 to modulate dormancy in salivary gland adenoid cystic carcinoma cells.Experimental & molecular medicine · 2025Article
- Article
- Cancer-associated fibroblasts as mediators of tissue microenvironment remodeling in cancer.Current opinion in cell biology · 2025Review
- New insights into extracellular vesicles in metastatic cancer: From mechanisms to diagnostics and targeted therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- LAMP1 as a Target for PET Imaging in Adenocarcinoma Xenograft Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Predictive effect and clinical diagnosis significance of exosome-related genes for nonalcoholic fatty liver disease-related hepatocellular carcinoma.Scientific reports · 2025Article
- Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma.Discover oncology · 2025Article
- Article
- Heat Shock Strengthens the Protective Potential of MSCs in Liver Injury by Promoting EV Release Through Upregulated Autophagosome Formation.Journal of extracellular vesicles · 2025Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) as a predominant cell component in the tumour microenvironment (TME) play an essential role in tumour progression. Our earlier studies revealed oxidized ATM activation in breast CAFs, which is independent of DNA double-strand breaks (DSBs). Oxidized ATM has been found to serve as a redox sensor to maintain cellular redox homeostasis. However, whether and how oxidized ATM in breast CAFs regulates breast cancer progression remains poorly understood. In this study, we found that oxidized ATM phosphorylates BNIP3 to induce autophagosome accumulation and exosome release from hypoxic breast CAFs. Inhibition of oxidized ATM kinase by KU60019 (a small-molecule inhibitor of activated ATM) or shRNA-mediated knockdown of endogenous ATM or BNIP3 blocks autophagy and exosome release from hypoxic CAFs. We also show that oxidized ATM phosphorylates ATP6V1G1, a core proton pump in maintaining lysosomal acidification, leading to lysosomal dysfunction and autophagosome fusion with multi-vesicular bodies (MVB) but not lysosomes to facilitate exosome release. Furthermore, autophagy-associated GPR64 is enriched in hypoxic CAFs-derived exosomes, which stimulates the non-canonical NF-κB signalling to upregulate MMP9 and IL-8 in recipient breast cancer cells, enabling cancer cells to acquire enhanced invasive abilities. Collectively, these results provide novel insights into the role of stromal CAFs in promoting tumour progression and reveal a new function of oxidized ATM in regulating autophagy and exosome release.
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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 Socratic graph.