Atypical protein kinase Cι as a human oncogene and therapeutic target

Biochem Pharmacol. 2014 Mar 1;88(1):1-11. doi: 10.1016/j.bcp.2013.10.023. Epub 2013 Nov 11.


Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family. The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions. Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer.

Keywords: Atypical Protein Kinase Cι; Cellular transformation; Mechanism-based therapeutics; Oncogenic signaling; Phox-Bem1 (PB1) domain.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / genetics*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Oncogenes / drug effects*
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / genetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects


  • Isoenzymes
  • Protein Kinase Inhibitors
  • Protein Kinase C
  • protein kinase C lambda