ArticleNeuroendocrinology2021
Modulation of Pancreatic Neuroendocrine Neoplastic Cell Fate by Autophagy-Mediated Death.
Article in Neuroendocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Photon irradiation prompts autophagy in anaplastic thyroid cancer.BMC cancer · 2026Article
- Tumor stage-dependent expression of autophagy proteins in adrenocortical carcinoma.Frontiers in endocrinology · 2026Article
- Leptin-dependent fat accumulation triggers autophagy in metabolic dysfunction-associated steatohepatitis model.Translational gastroenterology and hepatology · 2026Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.Endocrine · 2024Article
- Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions.Cancers · 2023Review
- Toll-like receptor 5 tunes hepatic and pancreatic stellate cells activation.BMJ open gastroenterology · 2023Article
- The Expression of Autophagy-Associated Genes Represents a Valid Footprint for Aggressive Pancreatic Neuroendocrine Neoplasms.International journal of molecular sciences · 2023Article
- Review
- Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma.Scientific reports · 2022Article
- Metformin promotes histone deacetylation of optineurin and suppresses tumour growth through autophagy inhibition in ocular melanoma.Clinical and translational medicine · 2022Article
- 3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs.Cancers · 2021Review
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
introductionAutophagic cell death in cancer cells can be mediated by inhibition of deacetylases. Although extensive studies have focused on the autophagic process in cancer, little is known about the role of autophagy in degrading cytosolic and nuclear components of pancreatic neuroendocrine neoplastic (pNEN) cells leading to cell death, thus improving the therapy of patients affected by pNEN.
methods2D and 3D human pNEN and pancreatic stellate cells were treated with panobinostat and bafilomycin. Autophagy markers were detected by RT-qPCR, immunofluorescence, and Western blot. Autophagosomes were detected by electron microscopy and their maturation by real-time fluorescence of LC3B stable transfected cells. ChIP was performed at the cAMP responsive element. Immunofluorescence was performed in murine pancreatic tissue.
resultsWe observed that pan-deacetylase inhibitor panobinostat treatment causes autophagic cell death in pNEN cells. We also found that although AMPK-α phosphorylation is counterbalanced by phosphorylated AKT, it is not capable to inhibiting autophagic cell death. However, the binding activity of the cAMP responsive element is prompted by panobinostat. Although autophagy inhibition prevented autophagosome synthesis, maturation, and cell death, panobinostat treatment induced the accumulation of mature autophagosomes in the cytosol and the nucleus, leading to disruption of the organelles, cellular digestion, and decay. Observation of autophagosome membrane proteins Beclin1 and LC3B aggregation in murine pancreatic islets indicates that autophagy restoration may also lead to autophagosome aggregation in murine insulinoma cells. A basal low expression of autophagy markers was detectable in patients affected by pNEN, and, interestingly, the expression of these markers was significantly lower in metastatic pNEN. DISCUSSION/
conclusionOur study highlights that the autophagy functional restoration and prolongation of this catabolic process, mediated by inhibition of deacetylase, is responsible for the reduction of pNEN cells. Prompting of autophagy cell death could be a promising strategy for the therapy of pNEN.
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