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Editorial
. 2018 Feb 20;118(4):459-461.
doi: 10.1038/bjc.2018.1. Epub 2018 Feb 20.

Protein Kinase D1: Gatekeeper of the Epithelial Phenotype and Key Regulator of Cancer Metastasis?

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Free PMC article
Editorial

Protein Kinase D1: Gatekeeper of the Epithelial Phenotype and Key Regulator of Cancer Metastasis?

Peter Storz. Br J Cancer. .
Free PMC article

Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Roles of PKD1 in maintaining the epithelial phenotype. Shown are some of the key events that are regulated by PKD1 and that prevent EMT and decrease cell motility. PKD1 blocks actin cytoskeleton rearrangements needed for cell movement through phosphorylation of SSH1L (inactivation) and PAK4 (activation), with a net effect of inhibiting cofilin. PKD1 also affects filopodia formation and length through phosphorylation of VASP, as well as focal adhesion dynamics by targeting PIP5K1γ and VASP. EMT and remodelling of the extracellular matrix are regulated through phosphorylation and proteasomal degradation of Snail, and by inhibition of MMP expression. In addition to increasing E-cadherin expression through inactivation of Snail, PKD1 also regulates the formation of E-cadherin-mediated cell–cell connections through phosphorylation of MTA1 and β-catenin, leading to MTA1 proteasomal degradation and β-catenin location to the E-cadherin complexes. EMT=epithelial-to-mesenchymal transition; MMPs=matrix metalloproteinases; MTA1=metastasis-associated protein 1; PKD1=protein kinase D1.

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