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. 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?

Free PMC article

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.


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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    1. Bastea LI, Doppler H, Balogun B, Storz P (2012) Protein kinase D1 maintains the epithelial phenotype by inducing a DNA-bound, inactive SNAI1 transcriptional repressor complex. PLoS One 7(1): e30459. - PMC - PubMed
    1. Borges S, Doppler H, Perez EA, Andorfer CA, Sun Z, Anastasiadis PZ, Thompson E, Geiger XJ, Storz P (2013) Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis. Breast Cancer Res 15(2): R66. - PMC - PubMed
    1. Borges S, Perez EA, Thompson EA, Radisky DC, Geiger XJ, Storz P (2015) Effective targeting of estrogen receptor-negative breast cancers with the protein kinase D inhibitor CRT0066101. Mol Cancer Ther 14(6): 1306–1316. - PMC - PubMed
    1. Bravo-Cordero JJ, Magalhaes MA, Eddy RJ, Hodgson L, Condeelis J (2013) Functions of cofilin in cell locomotion and invasion. Nat Rev Mol Cell Biol 14(7): 405–415. - PMC - PubMed
    1. Doppler H, Bastea LI, Borges S, Spratley SJ, Pearce SE, Storz P (2014) Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration. PLoS One 9(5): e98090. - PMC - PubMed