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Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer

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Abstract

The protein kinase D (PKD) family members, PKD1, PKD2 and PKD3 constitute a family of serine/threonine kinases that are essential regulators of cell migration, proliferation and protein transport. Multiple types of cancers are characterized by aberrant expression of PKD isoforms. In breast cancer PKD isoforms exhibit distinct expression patterns and regulate various oncogenic processes. In highly invasive breast cancer, the leading cause of cancer-associated deaths in females, the loss of PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 have been shown to be positive regulators of proliferation, chemoresistance and metastasis. In this review, we examine the differential expression pattern, mechanisms of regulation and contributions made by each PKD isoform to the development and maintenance of invasive breast cancer. In addition, we discuss the potential therapeutic approaches for targeting PKD in this disease.

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Abbreviations

CaMK:

Calcium/calmodulin-dependent kinase

CML:

Chronic myelogenous leukemia

S6K1:

S6 Kinase 1

DMTI:

DNA methyltransferase inhibitors

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial to mesenchymal transition

ER:

Estrogen receptor

ERE:

Estrogen response element

GABP:

GA-binding protein

GIT1:

G-protein-coupled receptor kinase-interacting protein 1

IDC:

Invasive ductal carcinoma

LIMK:

LIM domain kinase

MMP:

Matrix metalloproteinase

mTORC1:

Mammalian target of rapamycin complex 1

PAK4:

p21-activated kinase 4

PDZ:

Postsynaptic density 95/Discs large/zona occludens 1

PKC:

Protein kinase C

PKD:

Protein kinase D

RIN1:

Ras and Rab interactor 1

SSH1L:

Slingshot 1L

TNBC:

Triple-negative breast cancer

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Acknowledgments

This work was supported by the NIH grants GM086435, CA184527 and a Pilot Project grant from the Mayo Clinic Breast Cancer SPORE (CA116201-03DR4) to PS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The funders had no role in decision to publish, or preparation of the manuscript.

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  1. Department of Cancer Biology, Mayo Clinic, Griffin Room 306, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Nisha Durand, Sahra Borges & Peter Storz

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  1. Nisha Durand
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Durand, N., Borges, S. & Storz, P. Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer. Cell. Mol. Life Sci. 72, 4369–4382 (2015). https://doi.org/10.1007/s00018-015-2011-2

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