GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE291nnn/GSE291889/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291889GEOGSEfalsec-Rel drives pancreatic cancer metastasis through Fibronectin-Integrin signaling-induced isolation stress resistance and EMT activation [Cut&Run]Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, with limited treatment options and a high recurrence rate. Recurrence happens often with metastasis, for which cancer cells must adapt to isolation stress to successfully colonize distant organs. While the fibronectin-integrin axis has been implicated in this adaptation, its regulatory mechanisms require further elaboration. Here, we identify c-Rel as an oncogenic driver in PDAC, promoting epithelial-to-mesenchymal transition (EMT) plasticity, extracellular matrix (ECM) remodeling, and resistance to isolation stress. Mechanistically, c-Rel directly regulates fibronectin (Fn1) and CD61 (itgb3) transcription, enhancing cellular plasticity and survival under anchorage-independent conditions. Fibronectin is not essential for EMT, but its absence significantly impairs metastatic colonization, highlighting a tumor-autonomous role for FN1 in isolation stress adaptation. These findings establish c-Rel as a key regulator of PDAC metastasis by controlling circulating tumor cell (CTC) niche and survival, suggesting that targeting the c-Rel–fibronectin–integrin axis could provide new therapeutic strategies to mitigate disease progression and recurrence.2026/03/11GSE291889GSM884401434290291889Mus musculus[41398670]