ArticleJournal of hematology & oncology2025
Disruption of the sorcin‒PAX5 protein‒protein interaction induces ferroptosis by promoting the FBXL12-mediated ubiquitination of ALDH1A1 in pancreatic cancer.
Article in Journal of hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Tripterine Liposome Exerts Antitumor and Immunomodulatory Effects in Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- A targetable ALDH3A2-NRF2 axis mediates KEAP1-mutant tumour development via ferroptosis inhibition.Cell death and differentiation · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- SIRT6-Mediated Deacetylation of ATF3 Promotes Silica-Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FerroScore: a statistical approach for quantifying tumor-related ferroptosis based on omics data.Briefings in bioinformatics · 2026Article
- The Antitumor Potential of Celastrol: Research Progress on Antitumor Mechanisms and Strategies for Toxicity Reduction with Efficacy Enhancement.Biomolecules · 2026Review
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- SETD7-mediated H3K4me1 activates ALDH1A3 to drive ferroptosis resistance in esophageal squamous cell carcinoma.Cell death & disease · 2025Article
- Biochemical and Histological Characterization of Sorcin Overexpression in Patients Who Underwent Radical Prostatectomy.Urology research & practice · 2025Article
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7 authors.
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Abstract
backgroundPancreatic cancer is one of the most malignant cancers, and limited therapeutic options are available. The induction of ferroptosis is considered to be a novel, promising strategy that has potential in cancer treatment, and ferroptosis inducers may be new options for eradicating malignant cancers that are resistant to traditional drugs. The exact mechanism underlying the function of sorcin in the initiation and progression of pancreatic cancer remains unclear.
methodsThe expression of sorcin in cancer tissues was assessed by analyzing TCGA, GEO and immunohistochemical staining data, and the function of sorcin in the induction of ferroptosis in pancreatic cancer cells was investigated. The mechanism underlying the function of sorcin was revealed through proteomics, co-IP, Ch-IP, and luciferase assays. Natural product screening was subsequently performed to screen for products that interact with sorcin to identify new ferroptosis inducers.
resultsWe first showed that sorcin expression was positively correlated with the survival and tumor stages of patients with pancreatic cancer, and we revealed that sorcin inhibited ferroptosis through its noncalcium binding function. Furthermore, we discovered that sorcin interacted with PAX5 in the cytoplasm and inhibited PAX5 nuclear translocation, which in turn decreased FBXL12 protein expression and then reduced ALDH1A1 ubiquitination, thus inhibiting ferroptosis. Moreover, an in-house natural product screen revealed that celastrol inhibited the interaction of sorcin and PAX5 by directly binding to the Cys194 residue of the sorcin protein; disruption of the sorcin-PAX5 interaction promoted the nuclear translocation of PAX5, induced the expression of FBXL12, increased the ubiquitylation of ALDH1A1, and eventually induced ferroptosis in pancreatic cancer cells.
conclusionIn this study, we revealed the mechanism of action of sorcin, which is a druggable target for inducing ferroptosis, we identified celastrol as a novel agent that induces ferroptosis, and we showed that disrupting the sorcin-PAX5 interaction is a promising therapeutic strategy for treating pancreatic cancer.
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