KLF5 interacts with RUVBL1/2 to activate classical and basal lineage identities in PDAC [SLAM-seq]

We identify KLF5 as a lineage master regulator and a dependency in classical and basal subtypes of human PDAC. We integrate proteomic and genetic screens to reveal RUVBL1 and RUVBL2 as transcriptional coactivators of KLF5 in PDAC. We use biochemical and epigenomic methods to validate that KLF5-RUVBL1/2 complexes directly activate lineage identity genes in PDAC. Overall design: SLAM-seq following KLF5 degradation or RUVBL1/2 inhibition in basal-like and classical human pancreatic cancer cell lines.