KiSS1R, a G-protein coupled receptor (GPCR), and its ligands, collectively known as the kisspeptins, were originally discovered to have anti-metastatic effects. In melanoma, the expression of KiSS1R and the kisspeptins correlates with positive prognosis. However, in breast tumors, higher mRNA expression of KiSS1R and kisspeptins has been shown to correlate with progressing tumour grade. In large, the mechanism(s) by which kisspeptin-signaling via KiSS1R regulates breast cancer cell migration and invasion, required for metastasis, is unknown, and is the focus of this study. Commonly targeted in breast cancer therapy, aberrant signaling of the epidermal growth factor receptor (EGFR) is able to lead to increased migration and invasion, culminating in a more aggressive metastatic phenotype. EGFR's ability to interact with other GPCRs, whether directly by transactivation or indirectly by down-stream crosstalk, is well known. We have found that Kp-10, the most potent kisspeptin, stimulates the migration and invasion of highly invasive human MDA-MB-231 cells stably expressing FLAG-KiSS1R. In addition, we have observed co-localization of FLAG-KiSS1R and EGFR-GFP in human embryonic kidney (HEK 293) cells in response to Kp-10 or EGF stimulation. Stimulation of MDA-MB-231 cells with Kp-10 resulted in the activation of EGFR. Taken together, our findings suggest a potential mechanism by which kisspeptins and KiSS1R may stimulate breast cancer cell migration and invasion.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5213.