ENAGenomicsTHE OHIO STATE UNIVERSITYhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1283949We demonstrate the regulator of G protein signaling (RGS) 11 is a key target of CNT1 that by itself exerts potent tumor suppressive properties in Pancreatic ductal adenocarcinoma (PDAC). Compared with the normal human pancreatic tissues, the expression of RGS11 is diminished in human PDAC tissues which correspond with the reduced survival times in patients.RGS11 levels reversibly modulated the epithelial-mesenchymal transition (EMT) states of human PDAC cell lines influencing the chemotherapeutic sensitivities of anti-PDAC drugs. Global transcriptomic analysis revealed RGS11 replenishment in PDAC cells to suppress CD44-directed stemness features with significant reprogramming of the PDAC oncogenic landscape. Furthermore, RGS11 reduced the primary tumor burden and metastatic occurrence in a mouse model of PDAC. Together, these findings uncover RGS11 as a key target of CNT1 that exhibits therapeutic potential for intervention of aggressive PDAC.ENAfalseRGS11 as a tumor suppressor in PDAC2025-07-042025-07-04PRJNA1283949