Protein kinase Cε: an oncogene and emerging tumor biomarker

Members of the protein kinase C (PKC) family have long been studied for their contributions to oncogenesis. Among the ten different isoforms of this family of serine/threonine kinases, protein kinase Cε (PKCε) is one of the best understood for its role as a transforming oncogene. In vitro, overexpression of PKCε has been demonstrated to increase proliferation, motility, and invasion of fibroblasts or immortalized epithelial cells. In addition, xenograft and transgenic animal models have clearly shown that overexpression of PKCε is tumorigenic resulting in metastatic disease. Perhaps most important in implicating the epsilon isoform in oncogenesis, PKCε has been found to be overexpressed in tumor-derived cell lines and histopathological tumor specimens from various organ sites. Combined, this body of work provides substantial evidence implicating PKCε as a transforming oncogene that plays a crucial role in establishing an aggressive metastatic phenotype. Reviewed here is the literature that has led to the current understanding of PKCε as an oncogene. Moreover, this review focuses on the PKCε-mediated signaling network for cell motility and explores the interaction of PKCε with three major PKCε signaling nodes: RhoA/C, Stat3 and Akt. Lastly, the emerging role of PKCε as a tumor biomarker is discussed.