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Protein kinase D2: a versatile player in cancer biology

Oncogene volume 37, pages 1263–1278 (2018)Cite this article

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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.

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Funding

Funding

This work was supported by the German Research Foundation (grants AZ.96/1-1 and AZ.96/1-3 to NA, grant SE.676/10-1 to TS), the German Cancer Aid (grant 109373 to TS), FP7 grant 259770 – LUNGTARGET (to JVL and TS) and IWT - Agentschap voor Innovatie door Wetenschap en Technologie (to MC).

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Authors and Affiliations

  1. Center for Internal Medicine I, University of Ulm, Ulm, Germany

    Ninel Azoitei, Alexander Becher & Thomas Seufferlein

  2. Laboratory for Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, Leuven Cancer Institute, KU Leuven, Leuven, Belgium

    Mathias Cobbaut & Johan Van Lint

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  1. Ninel Azoitei
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Correspondence to Ninel Azoitei.

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Azoitei, N., Cobbaut, M., Becher, A. et al. Protein kinase D2: a versatile player in cancer biology. Oncogene 37, 1263–1278 (2018). https://doi.org/10.1038/s41388-017-0052-8

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