ArticleJournal of cellular and molecular medicine2019
Sigma-1 receptor protects against ferroptosis in hepatocellular carcinoma cells.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 155 citations in OpenAlex.
- Mesenchymal Stem Cells Alleviate Crohn's Disease by Regulating CBS-Mediated Ferroptosis.Immunity, inflammation and disease · 2026Article
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- miR-188-5p accelerates intervertebral disc degeneration by mediating P4HB to regulate ferroptosis in nucleus pulposus cells.European journal of medical research · 2025Article
- Fluvoxamine Attenuates Blood-Brain Barrier Disruption in Drug-Resistance Epilepsy and inhibits Ferroptosis via the Sigma-1 Receptor-TAMM41 signaling in bEnd.3 cells.Molecular neurobiology · 2025Article
- Inhibition of dipeptidyl peptidase 9 improves sorafenib sensitivity by inducing ferroptosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2025Article
- Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells.Scientific reports · 2025Article
- SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer.Journal of translational medicine · 2025Article
- Ferroptosis: CD8Cell death discovery · 2025Review
- Sigma-1 Receptor Specific Biological Functions, Protective Role, and Therapeutic Potential in Cardiovascular Diseases.Cardiovascular toxicology · 2025Review
- Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression.Journal of molecular cell biology · 2025Article
- Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.Current protein & peptide science · 2025Review
- Harnessing the gut microbiome to modulate ferroptosis: a metabolic strategy for the treatment of digestive tract cancers.Frontiers in immunology · 2025Review
- Dysregulated bile acid metabolism drives lipid peroxidation and ferroptosis in NAFLD: therapeutic potential for traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Sigma-1 Receptor Rescues Autophagy Through AMPK/mTOR Signaling Pathway in Sepsis-Induced Acute Kidney Injury.International journal of general medicine · 2025Article
- Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer.Frontiers in oncology · 2025Review
- S1R mediates NRF2 dependent ferroptosis of renal tubular epithelial cells to promote renal fibrosis in diabetic nephropathy.International journal of medical sciences · 2025Article
- [Ferroptosis and liver diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Ferroptosis: insight into the treatment of hepatocellular carcinoma.Cancer cell international · 2024Review
- Article
- Central role of Sigma-1 receptor in ochratoxin A-induced ferroptosis.Archives of toxicology · 2024Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sigma-1 receptor (S1R) regulates reactive oxygen species (ROS) accumulation via nuclear factor erythroid 2-related factor 2 (NRF2), which plays a vital role in ferroptosis. Sorafenib is a strong inducer of ferroptosis but not of apoptosis. However, the mechanism of sorafenib-induced ferroptosis in hepatocellular carcinoma (HCC) remains unclear. In this study, we found for the first time that sorafenib induced most of S1Rs away from nucleus compared to control groups in Huh-7 cells, and ferrostatin-1 completely blocked the translocation. S1R protein expression, but not mRNA expression, in HCC cells was significantly up-regulated by sorafenib. Knockdown of NRF2, but not of p53 or hypoxia-inducible factor 1-alpha (HIF1α), markedly induced S1R mRNA expression in HCC cells. Inhibition of S1R (by RNAi or antagonists) increased sorafenib-induced HCC cell death in vitro and in vivo. Knockdown of S1R blocked the expression of glutathione peroxidase 4 (GPX4), one of the core targets of ferroptosis, in vitro and in vivo. Iron metabolism and lipid peroxidation increased in the S1R knockdown groups treated with sorafenib compared to the control counterpart. Ferritin heavy chain 1 (FTH1) and transferrin receotor protein 1 (TFR1), both of which are critical for iron metabolism, were markedly up-regulated in HCC cells treated with erastin and sorafenib, whereas knockdown of S1R inhibited these increases. In conclusion, we demonstrate that S1R protects HCC cells against sorafenib and subsequent ferroptosis. A better understanding of the role of S1R in ferroptosis may provide novel insight into this biological process.
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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.