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Identification of genes bound by NFAT5-SMADs complex

GSE252838 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/10/09 Platform GPL16417
Summary
Oncogenic KRAS is now considered a druggable target; however, multiple mechanisms contribute to the development of resistance to KRAS-targeted therapy. A significant factor in therapy resistance is the alteration in cell state or cellular plasticity, exemplified by the epithelial-to-mesenchymal transition (EMT) phenotype. In pancreatic ductal adenocarcinoma (PDAC), the negative correlation between addiction to oncogenic KRAS signaling and EMT has been observed, yet the role of cell plasticity and its underlying mechanisms in governing resistance remain unclear. Our findings reveal that the pivotal EMT driver, TGFβ, facilitates KRAS bypass in PDAC through the nuclear factor NFAT5. NFAT5 interacts with canonical TGFβ factors SMAD3 and SMAD4, inducing EMT and therapy resistance. To identify DNA bound by the NFAT5-SMADs complex, we conducted Chromatin IP followed by next-generation sequencing (ChIP-seq) using antibodies binding to NFAT5, SMAD2, SMAD3, and SMAD4.
Published in
NFAT5 governs cellular plasticity-driven resistance to KRAS-targeted therapy in pancreatic cancer
Deng D, Begum H, Liu T et al. · The Journal of experimental medicine 2024 · PMID 39432061 · doi:10.1084/jem.20240766
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Also filed as BioProject PRJNA1062799 and SRA study SRP482751. Searching any of these in the dataset finder brings you back here.

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