ArticleJournal of experimental & clinical cancer research : CR2024
CCT3/ACTN4/TFRC axis protects hepatocellular carcinoma cells from ferroptosis by inhibiting iron endocytosis.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- CRISPR Screen Reveals Pathways and Factors Driving Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma.Cancer medicine · 2026Article
- AKR1C3 Binds β-Trcp to Promote the Degradation of TFRC to Protect Hepatocellular Carcinoma From Ferroptosis.Cancer science · 2026Article
- Transferrin receptor 1: an emerging therapeutic target in cancer beyond iron metabolism.Cancer cell international · 2026Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.npj aging · 2026Review
- Knockdown of CCT2 inhibits the malignant progression of hepatocellular carcinoma cells by impairing STAT3 activation.Oncology reports · 2026Article
- Chaperonin in health and disease.Molecular biomedicine · 2026Review
- CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma.iScience · 2026Article
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Expression patterns and clinical implications of chaperonin subunit 3 mRNA and protein in laryngeal squamous cell carcinoma.World journal of clinical oncology · 2025Article
- Potential involvement of the KLF2-GPX4 axis in ferroptosis during S.aureus-induced osteomyelitis.Human genomics · 2025Article
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- MDM2 promotes CELF6 ubiquitination-dependent degradation to promote neuroblastoma cell proliferation.Cell death & disease · 2025Article
- Impact of iron deficiency on therapeutic outcomes in colorectal cancer patients: a single-center cohort study.Journal of translational medicine · 2025Article
- Mechanistic insights into post-translational modifications in hepatic fibrosis: pathogenic roles and therapeutic potentials.Journal of translational medicine · 2025Review
- LOXL1-AS1 suppresses ferroptosis in cervical cancer through m6A-dependent regulation of TFRC.Journal of molecular histology · 2025Article
- Review
- Circular RNA TFRC/SCD1 mRNA interaction regulates ferroptosis and metastasis in gastric cancer.Cell death & disease · 2025Article
- Chaperonins in Hepatocellular Carcinoma: Unveiling Their Role in Tumor Proliferation and Immune Modulation Through Multiomics Analysis.International journal of genomics · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Sorafenib is widely used in treating advanced hepatocellular carcinoma (HCC). However, its effectiveness in prolonging patient survival is limited by the development of drug resistance. To systematically investigate the resistance mechanisms of Sorafenib, an integrative analysis combining posttranslational modification (PTM) omics and CRISPR/Cas9 knockout library screening was conducted. This analysis identified ubiquitination at lysine 21 (K21) on chaperonin-containing TCP1 subunit 3 (CCT3) as being associated with Sorafenib resistance. Transcriptomic data from HCC patients treated with Sorafenib revealed that CCT3 expression was lower in responders compared to non-responders. Experimentally, inhibiting the expression of CCT3 sensitized HCC cells to Sorafenib and enhanced Sorafenib-induced ferroptosis. Additionally, CCT3 was found to interact with ACTN4, hindering the recycling of transferrin receptor protein 1 (TFRC) to the cell membrane, thus obstructing iron endocytosis. Mechanistically, the inhibition of ferroptosis by CCT3 depends on the deubiquitination of K6-linked non-degradative ubiquitination at its K21, which occurs upon Sorafenib treatment. Moreover, CCT3 knockdown enhanced the anti-tumor effects of Sorafenib in nude mice. In summary, we have identified a novel function of the chaperone protein. Targeting the CCT3/ACTN4/TFRC axis offers a promising strategy to enhance ferroptosis and overcome Sorafenib resistance in HCC.
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Registered trials
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