The Kiss-1/Kiss-1R complex as a negative regulator of cell motility and cancer metastasis

Metastasis is a complex multistep process that involves the impairment of cell-cell adhesion in the neoplastic epithelium, invasion into adjacent tissues and the dissemination of cancer cells through the lymphatic and haematogenous routes. The inhibition of the metastatic process at an early stage has become a hot topic in cancer research. The Kiss-1 gene, initially described as a suppressor of metastasis in malignant melanoma, encodes the Kiss-1 protein which can be processed to other peptides, e. g., Kisspeptin-10, Kisspeptin-13, Kisspeptin-14 and Kisspeptin-54. These peptides are endogenous ligands of the Kiss-1 receptor (Kiss-1R), a G protein-coupled receptor (GPR) also known as hOT7T175, AXOR12 or GPR54. The Kiss-1 gene has been suggested as a suppressor of metastasis in a various types of cancer, including gastric cancer, oesophageal carcinoma, pancreatic, ovarian, bladder and prostate cancer, through the regulation of cellular migration and invasion. In the current review, we summarise the current understanding of the role of Kiss-1 and Kiss-1R in cancer and cancer metastasis.