ArticleAutophagy2014
Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 120 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- Meta-Analysis of Polymyositis and Dermatomyositis Microarray Data Reveals Novel Genetic Biomarkers.Genes · 2019Pooled it
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Toll-like Receptor 3 as a Context-Dependent Molecular Switch in Epithelial Cancers: Balancing Cell Death and Tumor-Supportive Programs.International journal of molecular sciences · 2026Review
- Lipopolysaccharide suppresses lung metastasis by activating CD8BMC cancer · 2026Article
- Tumor-intrinsic PD-L1 drives lung cancer progression in response to TLR stimulation by promoting autophagy through the TRAF6-BECN1 signaling axis.Experimental hematology & oncology · 2026Article
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- TXNIP Suppresses Lung Cancer Progression by Inhibiting TRAF6-Mediated NF-κB Activation and Autophagy.Immune network · 2025Article
- Inflammasomes and autophagy in cancer: unlocking targeted therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- In vivo mechanisms of resveratrol liposomes in targeting the TLR4/NLRP3 pathway in lung cancer.Scientific reports · 2025Article
- The role of innate immunity triggered by HPV infection in promoting cervical lesions.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Co-inhibition of RAGE and TLR4 sensitizes pancreatic cancer to irreversible electroporation in mice by disrupting autophagy.Acta pharmacologica Sinica · 2025Article
- TUT7-Mediated Uridine Degradation of MCPIP1 in the Pterygium to Regulate TRAF6-Mediated Autophagy.Investigative ophthalmology & visual science · 2025Article
- Apelin/APJ: Another Player in the Cancer Biology Network.International journal of molecular sciences · 2025Review
- Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma.Discover oncology · 2025Article
- Autophagy in Tissue Repair and Regeneration.Cells · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Role of toll-like receptors in pulmonary immunity: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- SVIP reduces IGFBP-2 expression and inhibits glioblastoma progression via stabilizing PTEN.Cell death discovery · 2024Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection.2025
Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy contributes to the pathogenesis of cancer, whereas toll-like receptors (TLRs) also play an important role in cancer development and immune escape. However, little is known about the potential interaction between TLR signaling and autophagy in cancer cells. Here we show that autophagy induced by TLR4 or TLR3 activation enhances various cytokine productions through promoting TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) ubiquitination and thus facilitates migration and invasion of lung cancer cells. Stimulation of TLR4 and TLR3 with lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] respectively triggered autophagy in lung cancer cells. This was mediated by the adaptor protein, toll-like receptor adaptor molecule 1 (TICAM1/TRIF), and was required for TLR4- and TLR3-induced increases in the production of IL6, CCL2/MCP-1 [chemokine (C-C motif) ligand 2], CCL20/MIP-3α [chemokine (C-C motif) ligand 20], VEGFA (vascular endothelial growth factor A), and MMP2 [matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase)]. These cytokines appeared to be necessary for enhanced migration and invasion of lung cancer cells upon TLR activation. Remarkably, inhibition of autophagy by chemical or genetic approaches blocked TLR4- or TLR3-induced Lys63 (K63)-linked ubiquitination of TRAF6 that was essential for activation of MAPK and NFKB (nuclear factor of kappa light polypeptide gene enhancer in B-cells) pathways, both of which were involved in the increased production of the cytokines. Collectively, these results identify induction of autophagy by TLR4 and TLR3 as an important mechanism that drives lung cancer progression, and indicate that inhibition of autophagy may be a useful strategy in the treatment of 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.