ArticleCancer science2021
Connexin32 activates necroptosis through Src-mediated inhibition of caspase 8 in hepatocellular carcinoma.
Article in Cancer science, 2021. 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, 28 citations in OpenAlex.
- Ischemia-Reperfusion Injury in Free Flaps: Molecular Mechanisms and Protective Effects of Remote Ischemic Preconditioning.Journal of cellular and molecular medicine · 2025Trial
- CD95 ligand drives abdominal aortic aneurysm progression through Caspase-8-mediated GSDMD-dependent endothelial pyroptosis: modulation by SRC kinase.Apoptosis : an international journal on programmed cell death · 2026Article
- Shikonin in Hepatocellular Carcinoma: Bridging Metabolic Disruption and Immunomodulation.Journal of hepatocellular carcinoma · 2026Review
- Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies.International journal of pharmaceutics: X · 2025Article
- Coordination of innate immune responses by connexins.Frontiers in immunology · 2025Review
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
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- Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review).International journal of oncology · 2024Review
- Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications.Cancers · 2024Review
- Targeting caspase-8: a new strategy for combating hepatocellular carcinoma.Frontiers in immunology · 2024Review
- Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma.Journal of inflammation research · 2024Article
- Optimal tagging strategies for illuminating expression profiles of genes with different abundance in zebrafish.Communications biology · 2023Article
- Exploration and validation of a novel signature of seven necroptosis-related genes to improve the clinical outcome of hepatocellular carcinoma.BMC cancer · 2023Article
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
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- Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma.BMC gastroenterology · 2022Article
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- Construction of a Necroptosis-Related miRNA Signature for Predicting the Prognosis of Patients With Hepatocellular Carcinoma.Frontiers in genetics · 2022Article
- Identification of a Necroptosis-Related Prognostic Signature and Associated Regulatory Axis in Liver Hepatocellular Carcinoma.Disease markers · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Necroptosis is an alternative form of programmed cell death that generally occurs under apoptosis-deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis-resistant HCC cells with high Cx32 expression remains unknown. In this study, we found that Cx32 expression was positively correlated with the expression of necroptosis protein biomarkers in human HCC specimens, cell lines, and a xenograft model. Treatment with shikonin, a well-used necroptosis inducer, markedly caused necroptosis in HCC cells. Interestingly, overexpressed Cx32 exacerbated shikonin-induced necroptosis, but downregulation of Cx32 alleviated necroptosis in vitro and in vivo. Mechanistically, Cx32 was found to bind to Src and promote Src-mediated caspase 8 phosphorylation and inactivation, which ultimately reduced the activated caspase 8-mediated proteolysis of receptor-interacting serine-threonine protein kinase 1/3, the key molecule for necroptosis activation. In conclusion, we showed that Cx32 contributed to the activation of necroptosis in HCC cells through binding to Src and then mediating the inactivation of caspase 8. The present study suggested that necroptosis inducers could be more favorable than apoptosis inducers to eliminate HCC cells with high expression of Cx32.
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Registered trials
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