Atypical PKCι contributes to poor prognosis through loss of apical-basal polarity and Cyclin E overexpression in ovarian cancer

We show that atypical PKC iota, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKC iota protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKC iota DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKC iota proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKC iota protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKC iota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKC iota is a novel target for therapy.