ArticleCell death & disease2021
Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Association of HMGB1 expression with prognosis of non-small cell lung cancer: a systematic review and meta-analysis.BMC cancer · 2026Pooled it
- HMGB1 Post-Translational Modifications in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Current Evidence, Emerging Mechanistic Concepts, and Unresolved Questions.International journal of molecular sciences · 2026Review
- 17β-Estradiol Modulates Cancer Cell-Fibroblast Communication via Autophagy-Mediated Extracellular Vesicle Secretion and Promotes Poor Prognosis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Secretory autophagy mediates SLC16A3/MCT4-dependent lactate secretion to drive metastatic progression in triple-negative breast cancer.Autophagy · 2026Article
- Cancer-associated fibroblasts promote osimertinib resistance in non-small cell lung cancer cells via METTL1-mediated NET1 mCell death & disease · 2026Article
- Blood-spinal cord barrier disruption after spinal cord injury: a time-dependent mechanistic review.Frontiers in cellular neuroscience · 2026Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- Peripheral blood tumor marker levels can indicate the location of lung cancer metastasis.Oncology letters · 2025Article
- Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation.Cancer medicine · 2025Review
- Article
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- Hidden forces: the impact of cancer-associated fibroblasts on non-small cell lung cancer development and therapy.Journal of translational medicine · 2025Review
- The role of the tumour microenvironment in lung cancer and its therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Effect of Benzyl Isothiocyanate on Anaplastic Thyroid Cancer Evaluated by Network Pharmacology Combined with Experiments.ACS omega · 2025Article
- Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to Metastasis via TGF-β Signalling Hyperactivation.Journal of extracellular vesicles · 2025Article
- The mechanism of high mobility group box-1 in the proliferation and macrophage polarization in esophageal squamous cell carcinoma cells.European journal of medical research · 2025Article
- Molecular mechanisms and pathological implications of unconventional protein secretion in human disease: from cellular stress to therapeutic targeting.Molecular biology reports · 2025Review
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Cancer-associated Fibroblasts Confer Osimertinib Resistance in Non-small Cell Lung Cancer Cells via NRG1-mediated HER3/AKT Signaling.Journal of Cancer · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Here, we reported that autophagy was upregulated in lung cancer-associated CAFs compared to normal fibroblasts (NFs), and autophagy was responsible for the promoting effect of CAFs on non-small cell lung cancer (NSCLC) cell migration and invasion. Inhibition of CAFs autophagy attenuated their regulation on epithelial-mesenchymal transition (EMT) and metastasis-related genes of NSCLC cells. High mobility group box 1 (HMGB1) secreted by CAFs mediated CAFs' effect on lung cancer cell invasion, demonstrated by using recombinant HMGB1, HMGB1 neutralizing antibody, and HMGB1 inhibitor glycyrrhizin (GA). Importantly, the autophagy blockade of CAFs revealed that HMGB1 release was dependent on autophagy. We also found HMGB1 was responsible, at least in part, for autophagy activation of CAFs, suggesting CAFs remain active through an autocrine HMGB1 loop. Further study demonstrated that HMGB1 facilitated lung cancer cell invasion by activating the NFκB pathway. In a mouse xenograft model, the autophagy specific inhibitor chloroquine abolished the stimulating effect of CAFs on tumor growth. These results elucidated an oncogenic function for secretory autophagy in lung cancer-associated CAFs that promotes metastasis potential, and suggested HMGB1 as a novel therapeutic target.
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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 Socratic graph.