Project 467228

An increasingly recognized feature of cancer is its ability to make alterations to metabolism to meet the high energy demands of rapidly growing tumours. The ability to reprogram their metabolism also helps cancer cells to better adapt to stressful conditions imposed by new environments, thereby supporting the movement of cancer cells from one site in the body to another in a process known as metastasis. Reprogrammed metabolism in cancer cells may further promote metastasis by contributing to the activation of cancer-associated fibroblasts at the tumour site, yielding a group of cells capable of releasing proteins and nutrients that promote cancer progression and that prime the tumour environment for cell migration. Cellular metabolism is controlled in part by peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1a), whose activity is associated with generating mitochondria and producing energy in the mitochondria. Interestingly, studies have demonstrated that increased PGC-1a expression in breast cancer cells increases their ability to metastasize to the lung in mice. However, the way in which PGC-1a-mediated changes to metabolism impacts breast cancer metastasis is unknown. The objective of this project will be to investigate how PGC-1a-mediated reprogramming of metabolism contributes to breast cancer metastasis. To achieve this objective, a combination of cell lines and mouse models of breast cancer will be used to identify PGC-1a-mediated metabolic alterations and how these changes impact breast cancer cell survival, division, and migration. Overall, gaining a better understanding of altered metabolism in breast cancer may allow us to uncover metabolic vulnerabilities that can be therapeutically targeted to better treat this widespread disease.