Featured Grad Paper: Donna Cvetkovic

KISS1R Induces Invasiveness of Estrogen Receptor-Negative Human Mammary Epithelial and Breast Cancer Cells 


Cvetkovic D, Dragan M, Leith SJ, Mir ZM, Leong HS, Pampillo M, Babwah AV, Bhattacharya M.
Endocrinology. 2013 Mar 24. [Epub ahead of print]


Description of paper:

Breast cancer is the second leading cause of cancer-related deaths in Canadian women, with the majority of these deaths resulting from metastatic spread of cancer to other tissues. Kisspeptins, peptide products of the Kisspeptin-1 (KISS1) gene, are endogenous ligands for KISS1R, a G protein-coupled receptor. In many cancers, KISS1 acts as a metastasis suppressor. However, in human breast tumors, studies have shown that there is an increase in KISS1 and KISS1R mRNA levels that correlates with higher tumor grade, increased metastatic potential and poor patient prognosis.

We have previously shown that kisspeptin stimulates the migration and invasion of aggressive breast cancer cells, that are deficient of estrogen receptors by activating the epidermal growth factor receptor, a clinical target. Kisspeptin stimulates matrix metalloproteinases (MMP-9) secretion and activity. The mechanisms by which KISS1R regulates breast cancer cell migration and invasion, two processes required for metastasis remain largely undefined. In this Endocrinology paper, we show for the first time that KISS1R triggers invasion and induces extravasation, a prerequisite step in cancer metastasis, in vivo. We report that overexpression of KISS1R induces a mesenchymal (invasive) phenotype, stimulating an epithelial to mesenchymal like event. We also found that kisspeptin transactivates EGFR only in the estrogen receptor-negative cell lines, but fails to stimulate migration, invasion or EGFR transactivation in the estrogen receptor-positive breast cancer cell lines. Overall, our data suggests that the estrogen receptor status of mammary cells critically dictates the ability of KISS1R to induce an invasive phenotype, thus revealing that KISS1R maybe a novel clinical target for the treatment of breast cancer.

A video citation of Donna's work can be seen at
:   MedicalXpress

Donna CvetkovicDonna's Bio:

Having obtained a Bachelor of Medical Science with Honors Specialization in Physiology from the University of Western Ontario in 2010, I felt that pursuing a graduate degree in Physiology was an appropriate continuation to my education. In the summer of 2010, I joined Dr. Bhattacharya’s laboratory that studies breast cancer. I was particularly interested in becoming a member of this dynamic laboratory due to a vested personal interest given that I had a front-view-seat to the course of this terrible disease and the damage this illness spreads not only to those afflicted but also those around them. Subsequently, I decided to start a Master’s program in Physiology in the Bhattacharya lab in September 2010. I was fortunate to start my graduate studies receiving a studentship from the Translational Breast Cancer Research Institute (TBCRU) from the London Regional Cancer Program (London, ON). The following year I was rewarded with studentships TBCRU and CIHR Strategic Training Program (STP) in Cancer Research and Technology Transfer (CaRTT). My participation in the CaRTT program had benefited me greatly because of the exposure I had received through the Translational Breast Cancer Research Seminars, which serve as a facilitator for the interactions between researchers studying cancer biology. In addition, I was fortunate to take the technology transfer course offered by the Business School that exposed me to partnerships with the private sector in translating new discoveries into clinical practice. In August of 2012 I had successfully defended my thesis and graduated with a Master of Science in Physiology. In addition to my interest in pursuing a M.Sc. degree in health-related field, I have had an opportunity to get involved in the community by volunteering at the operating room and emergency room departments at the London Health Science Center’s University Hospital. My volunteering experience has given me an insight of how to deal with patients and their families. The scientific aspect of diagnostics in conjunction with resolving clinical dilemmas as well as the interaction with patients, their families, and medical personnel is what makes medicine so fascinating. For my future endeavours, I am interested in combining my background in basic research with business to enlist the assistance of the private sector in translating new technology into clinical and community practice.


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