Kisspeptins, peptide products of KISS1, are endogenous ligands for KISS1R, a G protein-coupled receptor. In numerous cancers, KISS1 acts as a metastasis suppressor. However, studies have revealed that patients with elevated KISS1 and KISS1R breast tumor expression have increased tumor grade, increased lymph node metastases and poor survival. We hypothesize that depletion of KISS1R inhibits breast cancer cell metastasis. In order to assess the role of KISS1R in breast cancer metastasis, we used a pre-clinical orthotopic xenograft mouse model using MDA-MB-231 breast cancer cells for breast tumor establishment. We discovered that depletion of KISS1R decreased primary tumor growth and reduced lung metastatic burden, suggesting that KISS1R plays a role in promoting breast cancer metastasis. Furthermore, we observed that kisspeptin-10 stimulation increased breast cancer cell invadopodia formation via a β-arrestin2 dependent mechanism. Overall, our results suggest that KISS1R may be a novel therapeutic target in the prevention of breast cancer metastasis
