Background/Aim: 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. Materials and Methods: 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 fluorescentsubstrate 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. Results: 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. Conclusion: 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.Colorectal cancer (CRC) is the second deadliest malignancy for all the human population. The lifetime risk of developing CRC is about 1 in 23 for men and 1 in 25 women, while it has been shown that it is strongly associated with environmental and lifestyle factors, such as diet, tobacco, alcohol, androgen deprivation therapy, and obesity (1). A meta-analysis showed that elevated body mass index (BMI) is positively correlated with CRC development. There are several evidences for this association including changes in insulin-like growth factor 1 signaling, sex hormones, systemic inflammation and altered expression of adipokines (2).Adipose tissue not only regulates energy homeostasis, but is also a part of endocrine system secreting adipokines, growth factors, cytokines and chemokines. Adipokines are essential mediators of various metabolic processes, such as gluconeogenesis, glucose uptake, insulin signaling and fatty acid oxidation. During the development of obesity, the excess of adipose tissue results in increased adipokines secretion, that lead to protection against some of the adverse metabolic consequences of obesity (3). However, several studies have shown that increased level of adipokines, such as apelin, could be connected with higher probability to develop cancer, including gastroesophageal cell carcinoma (4), gastric cancer (5), non-small cell lung carcinoma (6), bladder cancer (7), prostate cancer (8), ovarian cancer (9), and breast cancer (10).The apelin-encoding gene (APLN) is located on...