ArticleAutophagy2016
Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Evidence on the link between hypothyroidism and non-alcoholic fatty liver disease: an updated systematic review.BMC endocrine disorders · 2025Pooled it
- The role of DAPK2 as a key regulatory element in various human cancers: a systematic review.Molecular biology reports · 2024Pooled it
- Identification of autophagy-related immune targets for enhancing immunotherapy in pancreatic cancer aggressiveness.Discover oncology · 2025Article
- Investigate of LOC101928988 Regulatory Effect on the DAPK2 Transcription in Breast Tumors.Cancer reports (Hoboken, N.J.) · 2025Article
- Fangchinoline attenuates hepatic fibrosis by regulating taurine metabolism and oxidative stress.Frontiers in pharmacology · 2025Article
- ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets.Frontiers in immunology · 2025Review
- The role of lipophagy in liver cancer: mechanisms and targeted therapeutic interventions.Frontiers in cell and developmental biology · 2025Review
- Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy.World journal of gastrointestinal pathophysiology · 2024Review
- Article
- Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System.International journal of molecular sciences · 2023Review
- Potential use of TG68 - A novel thyromimetic - for the treatment of non-alcoholic fatty liver (NAFLD)-associated hepatocarcinogenesis.Frontiers in oncology · 2023Article
- Review
- A Novel Noninvasive Diagnostic Model of HBV-Related Inflammation in Chronic Hepatitis B Virus Infection Patients With Concurrent Nonalcoholic Fatty Liver Disease.Frontiers in medicine · 2022Article
- mRNA-miRNA networks identify metabolic pathways associated to the anti-tumorigenic effect of thyroid hormone on preneoplastic nodules and hepatocellular carcinoma.Frontiers in oncology · 2022Article
- DAPK2 activates NF-κB through autophagy-dependent degradation of I-κBα during thyroid cancer development and progression.Annals of translational medicine · 2021Article
- Functional roles of non-coding RNAs regulated by thyroid hormones in liver cancer.Biomedical journal · 2021Review
- Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1.Signal transduction and targeted therapy · 2021Article
- Hypothyroidism Induces Interleukin-1-Dependent Autophagy Mechanism as a Key Mediator of Hippocampal Neuronal Apoptosis and Cognitive Decline in Postnatal Rats.Molecular neurobiology · 2021Article
- The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DEN-induced hepatotoxicity or carcinogenesis.
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