ArticleFrontiers in cell and developmental biology2021
Canonical and Non-canonical TGFβ Signaling Activate Autophagy in an ULK1-Dependent Manner.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Bta-miR-146a Inhibits Proliferation and Promotes Apoptosis of Bovine Immature Sertoli Cells by Targeting SMAD4 via the TGF-β/MAPK Signaling Pathway.International journal of molecular sciences · 2026Article
- TGF-β-induced autophagy in pulmonary artery endothelial cells associated with chronic thromboembolic pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2026Article
- From fibrotic mechanisms to clinical translation: the drug therapy revolution and delivery system breakthrough in proliferative vitreoretinopathy.Frontiers in immunology · 2026Review
- Prolonged Survival with Dieting for Improved Autophagy.Non-coding RNA · 2025Review
- Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.Nature communications · 2025Article
- Tacrolimus Modulates TGF-β Signaling-Related Genes and MicroRNAs in Human Retinal Pigment Epithelial Cells Activated by Lipopolysaccharide.International journal of molecular sciences · 2025Article
- Inhibiting the TGF-β1 Pathway Reduces the Aggressiveness of Intrahepatic CCA HuCCT1 CD90-Positive Cells.International journal of molecular sciences · 2025Article
- Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis.Vascular pharmacology · 2024Review
- PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization.Genome biology · 2024Article
- Tumor Necrosis Factor Receptor-Associated Factor 6 and Human Cancer: A Systematic Review of Mechanistic Insights, Functional Roles, and Therapeutic Potential.Journal of Cancer · 2024Review
- ULK1 Mediated Autophagy-Promoting Effects of Rutin-Loaded Chitosan Nanoparticles Contribute to the Activation of NF-κB Signaling Besides Inhibiting EMT in Hep3B Hepatoma Cells.International journal of nanomedicine · 2024Article
- Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review).International journal of molecular medicine · 2023Review
- Proton pump inhibitors display anti-tumour potential in glioma.Cell proliferation · 2023Review
- Regulation of TGF-Cancers · 2022Article
- Review
- Transforming growth factor-β in tumour development.Frontiers in molecular biosciences · 2022Review
- Autophagy regulated by the HIF/REDD1/mTORC1 signaling is progressively increased during erythroid differentiation under hypoxia.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The mechanism(s) in which transforming growth factor beta 1 (TGFβ) modulates autophagy in cancer remain unclear. Here, we characterized the TGFβ signaling pathways that induce autophagy in non-small cell lung cancer cells, using cells lines stably expressing GFP-LC3-RFP-LC3ΔG constructs that measure autophagic flux. We demonstrated that TGFβ1 increases Unc 51-like kinase 1 (ULK1) protein levels, 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent ULK1 phosphorylation at serine (S) 555 and ULK1 complex formation but decreases mechanistic target of rapamycin (mTOR) activity on ULK1. Further analysis revealed that the canonical Smad4 pathway and the non-canonical TGFβ activated kinase 1/tumor necrosis factor receptor-associated factor 6/P38 mitogen activated protein kinase (TAK1-TRAF6-P38 MAPK) pathway are important for TGFβ1-induced autophagy. The TAK1-TRAF6-P38 MAPK pathway was essential for downregulating mTOR S2448 phosphorylation, ULK1 S555 phosphorylation and autophagosome formation. Furthermore, although siRNA-mediated Smad4 silencing did not alter mTOR-dependent ULK1 S757 phosphorylation, it did reduce AMPK-dependent ULK1 S555 phosphorylation and autophagosome formation. Additionally, Smad4 silencing and inhibiting the TAK1-TRAF6-P38 MAPK pathway decreased autophagosome-lysosome co-localization in the presence of TGFβ. Our results suggest that the Smad4 and TAK1-TRAF6-P38 MAPK signaling pathways are essential for TGFβ-induced autophagy and provide specific targets for the inhibition of TGFβ in tumor cells that utilize autophagy in their epithelial-mesenchymal transition program.
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