Kisspeptin Inhibits Colorectal Cancer Cell Invasiveness by Activating PKR and PP2A

Abstract

BACKGROUND/AIM: The aim of the present study was to investigate the mechanism through which kisspeptin inhibits colorectal cancer metastasis. MATERIALS AND METHODS: Colorectal cancer cells were treated with kisspeptin and then subjected to assays for cell viability, migration, invasion and anchorage-independent growth. Kisspeptin receptor (KISS1R) requirement was examined by siRNA-based gene silencing followed by western blot and invasion assays. Kisspeptin regulation of PKR and PP2A was examined by treating cells with inhibitors for PKR or PP2A. RESULTS: Kisspeptin inhibited colorectal cancer cell invasiveness without affecting cell proliferation. Kisspeptin required activation of KISS1R and resulted in activation of PKR and PP2A. PKR inhibitor blocked kisspeptin-induced PP2A phosphorylation, while PP2A inhibitor failed to block kisspeptin-induced PKR phosphorylation. CONCLUSION: Kisspeptin-mediated activation of PKR-PP2A inhibited colorectal cancer cell invasiveness.