ArticleLaboratory investigation; a journal of technical methods and pathology2013
OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma.
Article in Laboratory investigation; a journal of technical methods and pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 83 citations in OpenAlex.
- OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD.bioRxiv : the preprint server for biology · 2026Article
- Protein Expression Dynamics in Breast Cancer Cells Exposed to Nano-Encapsulated Tarin, the Taro Lectin.Pharmaceutics · 2026Article
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- Mitochondrial-Based Nanomedicine in Treatment of Liver Cancer.Molecular biotechnology · 2026Review
- Design, synthesis, and biological evaluation of KA7, a novel quinolone-based sorafenib analogue with potent anticancer and immunomodulatory activities.RSC advances · 2025Article
- Targeting CXCR6 Disrupts β-Catenin Signaling and Enhances Sorafenib Response in Hepatocellular Carcinoma.Cancers · 2025Article
- Small molecule OPA1 inhibitors amplify cytochrome c release and reverse cancer cells resistance to Bcl-2 inhibitors.Science advances · 2025Article
- Mitochondrial Dysfunction-Molecular Mechanisms and Potential Treatment approaches of Hepatocellular Carcinoma.Molecular and cellular biochemistry · 2025Review
- Mitochondrial Dynamics in Blood Cancer Development and Progression.Current pharmacology reports · 2025Review
- [Liver cancer treatment with mitochondrial homeostasis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma.The Yale journal of biology and medicine · 2023Article
- Article
- Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules · 2023Review
- Therapeutic efficacy of sorafenib and plant-derived phytochemicals in human colorectal cancer cells.BMC complementary medicine and therapies · 2023Article
- An autophagy-inducing stapled peptide promotes c-MET degradation and overrides adaptive resistance to sorafenib in c-METBiochemistry and biophysics reports · 2023Article
- Article
- Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma.Cancer science · 2022Article
- Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth.Journal of experimental & clinical cancer research : CR · 2022Article
- Recent advances in, and challenges of, designing OMA1 drug screens.Pharmacological research · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Sorafenib has been used to treat advanced hepatocellular carcinoma (HCC), but the underlying molecular mechanisms remain controversial and why some patients do not respond to this therapy is poorly understood. In this study, we show that sorafenib triggers cell growth inhibition and apoptosis in HCC cells by directly targeting the mitochondria. Treatment with sorafenib induces rapid mitochondrial fragmentation, which is associated with the deregulation of mitochondria fusion-related protein optic atrophy 1 (OPA1). Exposure of cells or isolated mitochondria to sorafenib substantially induces cytochrome c release. Our data indicate that siRNA-mediated OPA1 knockdown significantly sensitizes HCC cells to sorafenib-induced apoptosis. Furthermore, sorafenib has no apparent apoptotic toxicity to normal human primary hepatocytes. Sorafenib inhibits HCC xenograft tumor growth in vivo and murine xenograft tumor tissue analysis reveals mitochondria fusion protein. OPA1 expression levels are strongly downregulated by sorafenib treatment. Western blotting evaluation of patient HCC with matched non-tumor tissue samples demonstrates that OPA1 expression is decreased in up to 40% of HCC patients. Taken together, we have shown that sorafenib suppresses the tumorigenesis of HCC through the induction of mitochondrial injury via OPA1. Our results provide new insights into the pathogenesis of HCC and suggest that OPA1 is a novel therapeutic target in patients with HCC.
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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.