The Role of Apelin and Apelin Receptor Expression in Migration and Invasiveness of Colon Cancer Cells.

Abstract

Colon cancer is the second deadliest malignancy for human. Its correlation with obesity has led to an increasing number of studies focusing on the role of adipokines in colon cancer development. Apelin, which belongs to the family of adipokines, affects several pathological processes, including heart diseases, obesity and carcinogenesis. In this study, we examined the importance of apelin and apelin receptor (APJ) during motility regulation of colon cancer cells. Colon cancer cells with overexpression of apelin receptor, as well as cells with down-regulation of apelin were used in this study. Migration and invasion ability was tested using Transwell® filters. The proteolytic activity was analyzed with fluorescent-substrate degradation assay and gelatin zymography. We also used confocal microscopy to examine migratory protrusion formation and the localization of MT1-MMP. The levels of AKT and ERK kinases were evaluated using Western blotting assay. Overexpression of APJ receptor resulted in increased migration and invasion abilities through stimulation of migratory protrusion formation and proteolytic activity. These processes were mediated by PI3K/AKT and MAPK signaling pathways. Opposite effect was obtained when the level of apelin was down-regulated. The level of apelin and its receptor is strictly connected with regulation of migration and invasion of colon cancer cells. Therefore, apelinergic system seems to be a promising target for anti-cancer therapy.