PAF1 cooperates with YAP1 in metaplastic ducts to promote pancreatic cancer.

ABSTRACT: Acinar-to-ductal metaplasia (ADM) is a precursor lesion of pancreatic ductal adenocarcinoma (PDAC); however, the regulators of the ADM-mediated PDAC development and its targeting are poorly understood. RNA polymerase II-associated factor 1 (PAF1) maintains cancer stem cells leading to the aggressiveness of PDAC. In this study, we investigated whether PAF1 is required for the YAP1-mediated PDAC development and whether CA3 and verteporfin, small molecule inhibitors of YAP1/TEAD transcriptional activity, diminish pancreatic cancer (PC) cell growth by targeting the PAF1/YAP1 axis. Here, we demonstrated that PAF1 co-expresses and interacts with YAP1 specifically in metaplastic ducts of mouse cerulein- or Kras^G12D-induced ADM and human PDAC but not in the normal pancreas. PAF1 knockdo

SUBMITTER: Nimmakayala RK 

PROVIDER: S-EPMC9525575 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature