Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice.

Abstract

Protein kinase C iota (PKCι) functions as a bonafide human oncogene in lung and ovarian cancer and is required for KrasG12D-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 KrasG12D-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 KrasG12D-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.

• Authors: Kristin S Inman, Yi Liu, Michele L Scotti Buzhardt, Michael Leitges, Murli Krishna, Howard C Crawford, Alan P Fields, Nicole R Murray
• Journal: Cancers (Cancers (Basel)) Vol. 14 Issue 3 (Feb 04 2022) ISSN: 2072-6694 [Print] Switzerland
• PMID: 35159064 (Publication Type: Journal Article)