PKCδ and tissue transglutaminase are novel inhibitors of autophagy in pancreatic cancer cells

Bulent Ozpolat, Ugur Akar, Kapil Mehta, Gabriel Lopei-Berestein

Research output: Contribution to journalReview articlepeer-review

64 Scopus citations

Abstract

Apoptosis (type I) and autophagy (type II) are both highly regulated forms of programmed cell death and play crucial roles in physiological processes such as the development, homeostasis and selective, moderate to massive elimination of cells, if needed. Accumulating evidence suggests that cancer cells, including pancreatic cancer cells, in general tend to have reduced autophagy relative to their normal counterparts and premalignant lesions, supporting the contention that defective autophagy provides resistance to metabolic stress such as hypoxia, acidity and chemotherapeutics, promotes tumor cell survival and plays a role in the process of tumorigenesis. However, the mechanisms underlying the reduced capability of undergoing autophagy in pancreatic cancer remain elusive. In a recent study, we demonstrated a novel mechanism for regulation of autophagy in pancreatic ductal carcinoma cells. We found that protein kinase C-delta (PKCδ) constitutively suppresses autophagy through induction of tissue transglutaminase (TG2). Inhibition of PKCδ/TG2 signaling resulted in significant autophagic cell death that was mediated by Beclin 1. Elevated expression of TG2 in pancreatic cancer cells has been implicated in the development of drug resistance, metastatic phenotype and poor patient prognosis. In conclusion, our data suggest a novel role of PKCδ/TG2 in regulation of autophagy, and that TG2 may serve as an excellent therapeutic target in pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)480-483
Number of pages4
JournalAutophagy
Volume3
Issue number5
DOIs
StatePublished - 2007

Keywords

  • Apoptosis
  • Autophagy
  • Pancreatic cancer
  • PKCδ
  • Rottlerin
  • TG2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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