Protein kinase D2: a versatile player in cancer biology

  • Oncogene. 2018 Mar;37(10):1263-1278. doi: 10.1038/s41388-017-0052-8.
Ninel Azoitei  1 ,  Mathias Cobbaut  2 ,  Alexander Becher  3 ,  Johan Van Lint  2 ,  Thomas Seufferlein  3
Affiliations
  • 1. Center for Internal Medicine I, University of Ulm, Ulm, Germany. [email protected].
  • 2. Laboratory for Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
  • 3. Center for Internal Medicine I, University of Ulm, Ulm, Germany.
PMID: 29259300 DOI: 10.1038/s41388-017-0052-8
Abstract

Protein kinase D2 (PKD2) is a serine/threonine kinase that belongs to the PKD family of calcium-calmodulin kinases, which comprises three isoforms: PKD1, PKD2, and PKD3. PKD2 is activated by many stimuli including growth factors, phorbol esters, and G-protein-coupled receptor agonists. PKD2 participation to uncontrolled growth, survival, neovascularization, metastasis, and invasion has been documented in various tumor types including pancreatic, colorectal, gastric, hepatic, lung, prostate, and breast Cancer, as well as glioma multiforme and leukemia. This review discusses the versatile functions of PKD2 from the perspective of Cancer hallmarks as described by Hanahan and Weinberg. The PKD2 status, signaling pathways affected in different tumor types and the molecular mechanisms that lead to tumorigenesis and tumor progression are presented. The latest developments of small-molecule inhibitors selective for PKD/PKD2, as well as the need for further chemotherapies that prevent, slow down, or eliminate tumors are also discussed in this review.