PKCι Is a Promising Prognosis Biomarker and Therapeutic Target for Pancreatic Cancer

Pathobiology. 2022;89(6):370-381. doi: 10.1159/000521588. Epub 2022 Jul 4.

Abstract

Background: As the highest prevalent pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) ranks the 7th lethal malignancy worldwide. The late diagnosis, chemotherapeutic resistance, and high associated mortality make PDAC a dilemma facing the oncologists. Protein kinase C (PKC) enzymes have been shown to be important in different cancer progression.

Methods: To understand the pattern of PKC enzymes in PDAC, we examined all PKC family member genes expression in PDAC and matched normal tissues. The critical role of PKCι was further investigated in different PDAC cells using cellular and molecular technology.

Results: We found that PRKCI (PKCι) was the most significantly overexpressed PKCs in pancreatic cancer. However, little is known about its role and regulation of oncogenic signaling pathways in pancreatic cancer. In this study, we confirmed the overexpression of PKCι in PDAC, and this high expression was associated with poor prognosis of patients. We proved that knockdown of PKCι by small interfering RNA or shRNA significantly inhibited pancreatic cancer cell growth and migration or invasion. Conversely, PKCι overexpression promoted pancreatic cancer cell growth and migration. Moreover, bioinformatical and technical studies informed the participation of PKCι in regression of apoptosis in PDAC cells, which may be related to the regulation of both PI3K/AKT and Wnt/β-catenin pathways.

Conclusions: Therefore, our results are adding more insight into the importance of PKCι in pancreatic cancer. PKCι induces pancreatic cancer progression through activation of PI3K/AKT and Wnt/β-catenin signaling pathways, which may provide a promising therapeutic target for pancreatic cancer.

Keywords: PI3K/AKT; PKCι; Pancreatic cancer; Protein kinase C; Wnt/β-catenin.

MeSH terms

  • Biomarkers
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Biomarkers
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • protein kinase C lambda