Marker-based CRISPR screening reveals a direct MED12-p63 interaction that activates basal identity in pancreatic ductal adenocarcinoma
We report a novel p63-MED12 transcriptional complex that is selectively required for basal pancreatic cancer and squamous cell carcinoma survival. This transcription factor-imposed genetic vulnerability on a general coactivator will inform future p63-blocking therapeutic strategies. Overall design: RNA-seq and ChIP-seq of p63 and MED12 manipulation in basal and classical human pancreatic cancer cell lines. FACS-based and negative selection CRISPR screens (genome-wide, Mediator exon tiling) to nominate lineage regulators of basal pancreatic cancer.