KiSS1 Suppresses Metastasis in Human Ovarian Cancer via Inhibition of Protein Kinase C Alpha

Abstract

Metastasis is a vital target for cancer treatment, since the majority of cancer patients die from metastatic, rather than the primary disease. KiSS1 has been identified as a metastasis suppressor gene in melanoma and breast carcinomas. We show here that KiSS1 is also a metastasis suppressor in human ovarian cancer. Overexpression of KiSS1 in ovarian cancer cells inhibits cell migration induced by serum or lysophosphatidic acid (LPA), and colonization in soft agar, but not cell proliferation, representing the characteristics of a metastasis suppressor gene. Furthermore, using an experimental metastatic mouse model, we show that expression of KiSS1 in SKOV3 ovarian cancer cells suppresses >50% metastatic colonization in mice (P < 0.0001). We find that activating protein kinase C (PKC) reverses about 80% of the inhibited cell migration induced by KiSS1, while down-regulation of PKCα with shRNA restores KiSS1 effect, providing evidence that inhibiting PKCα may be an important mechanism of the effect of KiSS1. These results suggest that KiSS1 is a metastasis suppressor of ovarian cancer and may be a potential molecular target for the treatment.