Mechanisms of Metformin-Induced c-MET Down-Regulation in Triple-Negative Breast Cancer

Over 250,000 new cases of invasive breast cancer are expected to be diagnosed in the United States each year. Triple-negative breast cancer is a breast cancer subtype that accounts for 20% of all breast cancers diagnosed. Approximately 50,000 new cases of triple-negative breast cancer are diagnosed each year. Triple-negative breast cancer is also noted as a health disparity, being that it is most common in African-American women.

Unfortunately, triple-negative breast cancer is associated with poor prognosis, often spreading to other tissues resulting in a mortality rate. This type of breast cancer is very difficult to treat because it lacks common markers targeted by cancer drugs. Therefore, scientists are developing new drugs to target molecular markers found in triple-negative breast cancers. This led to the testing of metformin, a drug already widely used to treat diabetes, for the treatment of triple-negative breast cancer.

Interestingly, scientists discovered that fewer diabetes patients taking metformin developed cancer over time. Although metformin is safe for patients to take, the mechanism by which metformin kills cancer cells is not fully understood. The objective of this study is to identify mechanisms of metformin-mediated regulation of c-MET regarding the inhibition of triple-negative breast cancer cells. Based on previous studies and our preliminary data, the researchers hypothesize that metformin inhibits basal-like/triple-negative breast cancer cells by down-regulation of c-MET signaling, which also regulates cell proliferation and cancer stem cell self-renewal.

The specific aims of this project are (1) to determine the effects of metformin-induced c-MET inhibition on TNBC cell growth and stemness, (2) to determine the molecular mechanism of metformin-induced c-MET down-regulation, and (3) to determine the impact of metformin-induced c-MET down-regulation on Wnt signaling in cancer stem cell stemness inhibition.

At the end of this project, the researchers hope to have an understanding of how metformin kills triple-negative breast cancer cells and how this can be translated to future animal and human studies. In addition to research project accomplishment, the researchers will also gain specific training in professional communication, grant writing, community outreach, and studies on cancer health disparity issues. Ultimately, the knowledge gained from their work will contribute to the elimination of cancer-related challenges associated with triple-negative breast and may be applied to other cancers to reduce the overall cancer burden.