# Mechanisms of metformin-induced c-MET downregulation in triple-negative breast cancer

> **NIH NIH F31** · NORTH CAROLINA CENTRAL UNIVERSITY · 2020 · $35,580

## Abstract

PROJECT SUMMARY
 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. With 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
investigate the mechanism of metformin-mediated c-MET regulation in its killing of basal like breast cancer
(BLBC)/TNBC cells. Based on previous studies and our preliminary data, we hypothesize that downregulation
of c-MET and the associated inhibition of cell proliferation and CSC self-renewal is a critical determinant of
metformin-mediated inhibition of basal-like/TNBC cells. The specific aims 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 downregulation; and 3) To determine the impact of metformin-
induced c-MET downregulation on Wnt signaling in cancer stem cell stemness inhibition. At the end of this
project, we 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, I
will also gain specific training in professional communication, grant writing, community outreach, and studies
on cancer health disparity issues. Ultimately, the knowledge gained from our 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.

## Key facts

- **NIH application ID:** 10048636
- **Project number:** 5F31CA239507-02
- **Recipient organization:** NORTH CAROLINA CENTRAL UNIVERSITY
- **Principal Investigator:** Dana Marie Austin Gant
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,580
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048636

## Citation

> US National Institutes of Health, RePORTER application 10048636, Mechanisms of metformin-induced c-MET downregulation in triple-negative breast cancer (5F31CA239507-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10048636. Licensed CC0.

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