Protein kinase D signaling in cancer: A friend or foe?

Protein kinase D is a family of evolutionarily conserved serine/threonine kinases that belongs to the Ca++/Calmodulin-dependent kinase superfamily. Signal transduction pathways mediated by PKD can be triggered by a variety of stimuli including G protein-coupled receptor agonists, growth factors, hormones, and cellular stresses. The regulatory mechanisms and physiological roles of PKD have been well documented including cell proliferation, survival, migration, angiogenesis, regulation of gene expression, and protein/membrane trafficking. However, its precise roles in disease progression, especially in cancer, remain elusive. A plethora of studies documented the cell- and tissue-specific expressions and functions of PKD in various cancer-associated biological processes, while the causes of the differential effects of PKD have not been thoroughly investigated. In this review, we have discussed the structural-functional properties, activation mechanisms, signaling pathways and physiological functions of PKD in the context of human cancer. Additionally, we have provided a comprehensive review of the reported tumor promoting or tumor suppressive functions of PKD in several major cancer types and discussed the discrepancies that have been raised on PKD as a major regulator of malignant transformation.