ArticleCancer immunology research2016
Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation.
Article in Cancer immunology research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research.Frontiers in physiology · 2020Pooled it
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- Autophagy: a novel target in order to overcome drug resistance in pancreatic adenocarcinoma.Open biology · 2025Review
- Integrating bioengineering, super-resolution microscopy and mechanobiology in autophagy research: addendum to the guidelines (4th edition).Autophagy · 2025Article
- Unveiling the physiological impact of ESCRT-dependent autophagosome closure by targeting the VPS37A ubiquitin E2 variant-like domain.Cell reports · 2024Article
- Mechanism of TBK1 activation in cancer cells.Cell insight · 2024Review
- Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis.Scientific reports · 2024Article
- Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies.Molecular cancer · 2023Review
- RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment.Journal of translational medicine · 2023Review
- Constitutively active autophagy in macrophages dampens inflammation through metabolic and post-transcriptional regulation of cytokine production.Cell reports · 2023Article
- Identification of Small GTPases That Phosphorylate IRF3 through TBK1 Activation Using an Active Mutant Library Screen.Biomolecules & therapeutics · 2023Article
- Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer.Frontiers in oncology · 2023Review
- Association between autophagy and acute pancreatitis.Frontiers in genetics · 2023Review
- Identification of 1Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Autophagy in Cancer Immunotherapy.Cells · 2022Review
- TBK1 is part of a galectin 8 dependent membrane damage recognition complex and drives autophagy upon Adenovirus endosomal escape.PLoS pathogens · 2022Article
- Novel Effects of Statins on Cancer via Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Autophagy in cancer cell remodeling and quality control.Molecular cell · 2022Review
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Article
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Autophagy promotes tumor progression downstream of oncogenic KRAS, yet also restrains inflammation and dysplasia through mechanisms that remain incompletely characterized. Understanding the basis of this paradox has important implications for the optimal targeting of autophagy in cancer. Using a mouse model of cerulein-induced pancreatitis, we found that loss of autophagy by deletion of Atg5 enhanced activation of the IκB kinase (IKK)-related kinase TBK1 in vivo, associated with increased neutrophil and T-cell infiltration and PD-L1 upregulation. Consistent with this observation, pharmacologic or genetic inhibition of autophagy in pancreatic ductal adenocarcinoma cells, including suppression of the autophagy receptors NDP52 or p62, prolonged TBK1 activation and increased expression of CCL5, IL6, and several other T-cell and neutrophil chemotactic cytokines in vitro Defective autophagy also promoted PD-L1 upregulation, which is particularly pronounced downstream of IFNγ signaling and involves JAK pathway activation. Treatment with the TBK1/IKKε/JAK inhibitor CYT387 (also known as momelotinib) not only inhibits autophagy, but also suppresses this feedback inflammation and reduces PD-L1 expression, limiting KRAS-driven pancreatic dysplasia. These findings could contribute to the dual role of autophagy in oncogenesis and have important consequences for its therapeutic targeting. Cancer Immunol Res; 4(6); 520-30. ©2016 AACR.
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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 OpenQuestion graph.