Inman KS, Liu Y, Scotti Buzhardt ML, Leitges M, Krishna M, Crawford HC, Fields AP, and Murray NR. Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice. Cancers (Basel) 2022; 14(3).
Protein kinase C iota (PKCι) functions as a bonafide human oncogene in lung and ovarian cancer and is required for Kras(G12D)-mediated lung cancer initiation and progression. PKCι expression is required for pancreatic cancer cell growth and maintenance of the transformed phenotype; however, nothing is known about the role of PKCι in pancreas development or pancreatic tumorigenesis. In this study, we investigated the effect of pancreas-specific ablation of PKCι expression on pancreatic cellular homeostasis, susceptibility to pancreatitis, and Kras(G12D)-mediated pancreatic cancer development. Knockout of pancreatic Prkci significantly increased pancreatic immune cell infiltration, acinar cell DNA damage, and apoptosis, but reduced sensitivity to caerulein-induced pancreatitis. Prkci-ablated pancreatic acinar cells exhibited P62 aggregation and a loss of autophagic vesicles. Loss of pancreatic Prkci promoted Kras(G12D)-mediated pancreatic intraepithelial neoplasia formation but blocked progression to adenocarcinoma, consistent with disruption of autophagy. Our results reveal a novel promotive role for PKCι in pancreatic epithelial cell autophagy and pancreatic cancer progression.