Protein kinase C epsilon: 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 C epsilon (PKC epsilon) is one of the best understood for its role as a transforming oncogene. In vitro, overexpression of PKC epsilon 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 PKC epsilon is tumorigenic resulting in metastatic disease. Perhaps most important in implicating the epsilon isoform in oncogenesis, PKC epsilon 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 PKC epsilon 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 PKC epsilon as an oncogene. Moreover, this review focuses on the PKC epsilon-mediated signaling network for cell motility and explores the interaction of PKC epsilon with three major PKC epsilon signaling nodes: RhoA/C, STAT3 and Akt. Lastly, the emerging role of PKC epsilon as a tumor biomarker is discussed.
Gorin
Michael A
MA
University of Miami, Miller School of Medicine, Miami, FL 33136, USA. magorin@med.miami.edu
Pan
Quintin
Q
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D011485:Protein Binding; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D014408:Biomarkers, Tumor; D051744:Protein Kinase C-epsilon