ArticleActa pharmacologica Sinica2024
SMAD4 endows TGF-β1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Ellagic Acid Enhances RSL3-Induced Ferroptosis by Inhibiting the Nrf2/HO-1 Signaling Pathway in Pancreatic Ductal Adenocarcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hypoxia Differentially Regulates Ferroptosis Sensitivity and Tumor Cell-Intrinsic Type I Interferon Signaling in Pancreatic Ductal Adenocarcinoma Cells.International journal of molecular sciences · 2026Article
- Effect of LY2109761 on TGF-β1/TGFβRI/Smad Pathway and Hepatic Fibrosis Cysts Formation in Rats Infected with Echinococcus granulosus: an In Vitro and In Vivo Study.Acta parasitologica · 2026Article
- MFAP2 secreted by TGF-β1-induced cancer-associated fibroblast cells promotes gastric cancer peritoneal metastasis through Src-STAT3-PTK7 axis.Cell death discovery · 2026Article
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Amelioration of colorectal cancer-associated fibroblasts in immunosuppressive microenvironment by ferroptosis-based nanotherapy.Nature communications · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Review
- SMAD4-armed oncolytic adenovirus therapy potentiates the chemotherapy effects in NSCLC through suppression of the Wnt/β-catenin pathway.Cancer gene therapy · 2025Article
- The influence of ferroptosis-associated gene HSPA5 on the prognosis and immune evasion of lung adenocarcinoma.Discover oncology · 2025Article
- The ACSS2-PPARD-BCAT1 axis synchronously regulates branched-chain amino acid metabolism and development in pancreatic cancer.Acta biochimica et biophysica Sinica · 2025Article
- Advances in the Regulation by Immune Cells of Skeletal Myositis Outcomes.Aging and disease · 2025Review
- The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.Biomolecules · 2025Review
- Machine learning and gene network integration reveal prognostic subnetworks and biomarkers in pancreatic cancer.Computational and structural biotechnology journal · 2025Article
- Nanomaterial-Driven Regulated Cell Death: Mechanistic Insights and Novel Strategies for Tumor Therapy.International journal of nanomedicine · 2025Review
- Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway.Respiratory research · 2024Article
- Glutathione Peroxidases: An Emerging and Promising Therapeutic Target for Pancreatic Cancer Treatment.Antioxidants (Basel, Switzerland) · 2024Review
- Integrating single-cell and spatial transcriptomic analysis to unveil heterogeneity in high-grade serous ovarian cancer.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor β (TGF-β) pathway, which affects the TGF-β-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor β1 (TGF-β1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-β1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.
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