GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338354/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338354GEOGSEfalsePRMT1-mediated arginine methylation redirects a metastasis-promoting transcriptional output of SMAD4 in pancreatic cancerPancreatic ductal adenocarcinoma (PDAC) is characterized by early metastatic dissemination and poor clinical outcomes. Although SMAD4 is frequently altered in PDAC, the majority of tumors retain wild-type SMAD4, which paradoxically acquires pro-metastatic functions during disease progression. How SMAD4 transcriptional output is reprogrammed to support metastasis in advanced PDAC remains poorly understood.Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical modifier that promotes a metastasis-promoting transcriptional state of SMAD4. PRMT1 catalyzes asymmetric dimethylation of SMAD4 at arginine 272 (R272), a modification that does not alter SMAD4 expression but stabilizes nuclear SMAD2/3-SMAD4 complexes and redirects SMAD4 chromatin engagement toward epithelial-mesenchymal transition (EMT) gene programs. Mechanistically, R272-methylated SMAD4 promotes the recruitment of a BRG1-CTCF transcriptional complex, enabling chromatin-dependent activation of pro-metastatic transcriptional outputs.Importantly, pharmacological inhibition of PRMT1, particularly in combination with BRG1 degradation, dismantles methylation-dependent SMAD4 transcriptional complexes, suppresses EMT programs, and markedly reduces liver metastasis in preclinical PDAC models.Together, these findings uncover a post-translational mechanism that governs SMAD4 transcriptional specificity and identify PRMT1-dependent methylation as a therapeutic vulnerability in SMAD4-wild-type pancreatic cancer.2026/07/16GSE338354GSM9871841GSM9871843GSM9871842GSM9871845GSM9871844GSM987184615433338354Homo sapiens