Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Normal, healthy cells have many mechanisms to prevent uncontrolled growth. Cancer cells evade these mechanisms and grow without control, leading to tumor development. One way in which both normal and cancerous cells grow is through the action of two proteins found on the surface of cells. These proteins are called Epidermal Growth Factor Receptor (EGFR) and insulin receptor (IR). In normal cells, EGFR and IR are only activated when they bind to growth factors that are present in the bloodstream, causing them to send signals to the cell to grow. In many cancers, such as the aggressive triple-negative breast cancer, EGFR/IR becomes aberrantly activated, which can cause cancer growth even with minimal or no growth factors, driving tumor progression and metastasis (cancer spread throughout the body). Current cancer treatments try to block EGFR/IR activity to slow down growth. While this can be an effective treatment, cancer cells have ways to become resistant to these treatments. There is also a poorly understood difference in the treatment outcomes following EGFR/IR inhibition among different patients. We have begun to show that not all EGFR/IR molecules within a cancer cell behave the same. Why the same receptors behave differently is unknown, but studying this is important to understand how these cancer-driving receptors work. We recently discovered that a family of proteins called tetraspanins form special environments on a cell that "gate" which EGFR proteins activate more readily than others. However, the mechanism(s) is poorly understood, limiting the development of new therapies. Our research aims to understand how both EGFR and IR are regulated by these tetraspanin proteins in clinically relevant contexts, and what this might mean for novel therapeutic strategies for triple-negative breast cancer. Understanding how EGFR and IR are regulated by tetraspanins paves the way to improve cancer therapies and find new mechanisms to prevent breast cancer resistance.