ArticleThe American journal of pathology2018
Chaperone-Mediated Autophagy Promotes Beclin1 Degradation in Persistently Infected Hepatitis C Virus Cell Culture.
Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Inflammasomes and autophagy in cancer: unlocking targeted therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- ATG5 negatively regulates grass carp reovirus-induced immune-inflammatory response by degrading RIG-I and MDA5.Journal of virology · 2025Article
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- A Single-Step Immunocapture Assay to Quantify HCC Exosomes Using the Highly Sensitive Fluorescence Nanoparticle-Tracking Analysis.Journal of hepatocellular carcinoma · 2023Article
- The Role of Macroautophagy and Chaperone-Mediated Autophagy in the Pathogenesis and Management of Hepatocellular Carcinoma.Cancers · 2022Review
- Impaired Autophagy Response in Hepatocellular Carcinomas Enriches Glypican-3 in Exosomes, Not in the Microvesicles.Journal of hepatocellular carcinoma · 2022Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- Extracellular Vesicle Release Promotes Viral Replication during Persistent HCV Infection.Cells · 2021Article
- Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021Review
- Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis.Journal of hepatocellular carcinoma · 2021Article
- The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis.Frontiers in cellular and infection microbiology · 2021Review
- Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases.Cancers · 2020Review
- Chaperone-mediated autophagy in cancer: Advances from bench to bedside.Histology and histopathology · 2020Review
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma.Frontiers in aging neuroscience · 2020Article
- Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.Journal of hepatocellular carcinoma · 2020Review
- Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.Frontiers in cell and developmental biology · 2020Review
- Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Liver cirrhosis is an independent risk factor for hepatocellular carcinoma (HCC). The mechanisms that contribute to HCC development in the cirrhotic microenvironment are unknown. We found that HCC grown in the highly stressed cirrhotic microenvironment undergoes autophagy switching from a protective state characterized by high macroautophagy with low chaperone-mediated autophagy (CMA) to an HCC-promoting state characterized by low macroautophagy with high CMA. This study examined how the stress response executes oncogenic cell programming through autophagy switching using hepatitis C virus cell culture. Protein kinase R-like endoplasmic reticulum kinase expression increased to high levels in hepatitis C virus culture. Protein kinase R-like endoplasmic reticulum kinase-dependent activation of nuclear factor erythroid 2-related factor (Nrf2) led to increased transcription of the cytoprotective genes: heat shock cognate 70 kDa protein and lysosome-associated membrane protein 2A (LAMP2A) and precipitated the induction of CMA. CMA selectively targeted beclin1 degradation, leading to accumulation of the autophagy flux protein p62 due to impaired autophagosome-endosome fusion. This impaired autophagosome-endosome fusion due to beclin1 degradation inhibited endocytosis and degradation of epidermal growth factor receptor. Silencing Nrf2 and LAMP2A reduced cell viability, suggesting that the stress response activates CMA as a compensatory mechanism of cell survival. We report a novel mechanism through which stress response triggers oncogenic Nrf2 signaling that promotes autophagy switching to favor cell survival.
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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.