Grant: Master's Award: Canada Graduate Scholarships

This year, almost 29,000 Canadian women will be diagnosed with breast cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that accounts for ~15% of these cases for which the prognosis remains poor. Tumor environments in TNBC exhibit differences in cell signaling and metabolism that lead to abnormal cell growth, survival, and migration. These tumors have limited access to key nutrients like amino acids. To combat nutrient restriction, TNBC cells have the ability to sense and adapt to amino acid insufficiency. TNBC cells achieve this by replenishing amino acids through protein recycling processes called autophagy and macropinocytosis. How cells monitor nutrients in the exceptional circumstances that trigger autophagy and macropinocytosis is poorly understood. In addition, GSK3? is a vital protein that regulates cell growth and metabolism. GSK3? has been shown to promote cancer cell growth when located in the cytoplasm and suppress cancer cell growth when located in the nucleus. This transport of GSK3? in and out of the nucleus is critical and tightly controlled by nutrient sensing complexes. One such complex includes a protein called DEPDC5 which has been found to sense amino acids in a unique manner in nutrient starved cancer cells that correlates with GSK3? movement into and out of the nucleus. This research aims to characterize the impact of this novel signaling axis to identify the molecular mechanisms at play when cancer cells activate autophagy and/or macropinocytosis to restore nutrients. Understanding how TNBC cells adapt to metabolic stress through GSK3? regulation may lead to the development of new and more effective treatments that selectively target key facets of this signaling axis to improve outcomes in cancers like TNBC.