Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Kristin S. Inman, Yi Liu, Michele L. Scotti Buzhardt, Michael Leitges, Murli Krishna, Howard H Crawford, Alan P. Fields, Nicole R Murray

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number796
JournalCancers
Volume14
Issue number3
DOIs
StatePublished - Feb 1 2022

Keywords

  • Autophagy
  • Immune cell infiltration
  • Pancreatic cancer
  • Protein kinase C iota
  • Tumor progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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