Date of Award


Degree Type


Degree Name

Master of Science


Pharmacology and Toxicology


Dr. Moshmi Bhattacharya

Second Advisor

Dr. John Di Guglielmo

Third Advisor

Dr. Susan Meakin


Kisspeptins, peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for GPR54, a G protein-coupled receptor. KISS1 encodes the metastasis suppressor of a large number of cancers. Recent studies, however, have shown that an increase in KISS1 and GPR54 expression in human breast tumours correlates with higher tumour grade. Whether kisspeptin signaling promotes breast cancer cell invasiveness is unknown. We found that Kisspeptin- 10 (Kp-10) stimulated the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Transwell chamber assays and induced the formation of invasive structures in three-dimensional Matrigel. The effect of Kp-10 on tumour cell invasion was blocked upon treatment of cells with epidermal growth factor receptor (EGFR) inhibitor AG 1478. Kp-10 stimulated the transactivation of EGFR via Src. We aso observed by co-immunoprecipitation that the two receptors associate with each other. Taken together, our findings suggest that kisspeptin/GPR54 signaling stimulates breast cancer cell invasiveness by transactivating EGFR.



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