ArticleThe Journal of experimental medicine2024
NFAT5 governs cellular plasticity-driven resistance to KRAS-targeted therapy in pancreatic cancer.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- High IntratumoralInternational journal of molecular sciences · 2026Pooled it
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification.Redox biology · 2026Review
- HDHD5 promotes triple-negative breast cancer growth and drives EMT-associated phenotypes via regulating S100A4.Journal of cancer research and clinical oncology · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- The Combination of a BCL-xL PROTAC and an mTOR Inhibitor Sensitizes Pancreatic Ductal Adenocarcinoma to KRASCancers · 2026Article
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- The combination of BCL-xL PROTAC and mTOR inhibitor sensitizes pancreatic ductal adenocarcinoma to KRASbioRxiv : the preprint server for biology · 2026Article
- Network pharmacology and experimental study on the inhibition of glycolysis by amentoflavone in pancreatic cancer.Discover oncology · 2025Article
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- PLAGL2 as a prognostic biomarker and an EMT-promoting factor in PDAC.Scientific reports · 2025Article
- Stromal Cells in Early Inflammation-Related Pancreatic Carcinogenesis-Biology and Its Potential Role in Therapeutic Targeting.Cancers · 2025Review
- Modulators of Alpha-2 Macroglobulin Upregulation by High Glucose in Glomerular Mesangial Cells.Biomolecules · 2024Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Resistance to KRAS therapy in pancreatic ductal adenocarcinoma (PDAC) involves cellular plasticity, particularly the epithelial-to-mesenchymal transition (EMT), which poses challenges for effective targeting. Chronic pancreatitis, a known risk factor for PDAC, elevates TGFβ levels in the tumor microenvironment (TME), promoting resistance to KRAS therapy. Mechanistically, TGFβ induces the formation of a novel protein complex composed of SMAD3, SMAD4, and the nuclear factor NFAT5, triggering EMT and resistance by activating key mediators such as S100A4. Inhibiting NFAT5 attenuates pancreatitis-induced resistance to KRAS inhibition and extends mouse survival. Additionally, TGFβ stimulates PDAC cells to secrete CCL2, recruiting macrophages that contribute to KRAS bypass through paracrine S100A4. Our findings elucidate the role of TGFβ signaling in EMT-associated KRAS therapy resistance and identify NFAT5 as a druggable target. Targeting NFAT5 could disrupt this regulatory network, offering a potential avenue for preventing resistance in PDAC.
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