Grant: Project Grant

The ability of breast cancer cells to spread from the primary tumor to distant sites in the body, a process called metastasis, is the most deadly aspect of this disease. Recent research has focused on how cancer cells meet the energy and building block requirements needed for rapid primary tumor growth. What has been less studied, is how cancer cell metabolism changes during metastasis. In addition, how the environment at distinct metastatic sites, such as the liver, influences breast cancer metabolism is unknown. We demonstrate that breast cancer cells increasingly rely on glycolytic metabolism as they progress from being tumorigenic to becoming highly metastatic. We hypothesize that in order for breast cancer cells to successfully metastasize, several metabolic adaptations must occur which engage different pathways in the cell. Metabolites refer to cellular by-products that can ultimately be used to fuel and stimulate breast cancer growth. We will assess whether metabolites produced by resident cells in the liver can fuel the growth of breast cancer cells that have metastasized to this organ. We will also address whether breast cancer cells can stimulate the production of such pro-tumorigenic metabolites from liver cells, which feed back to the tumor cells themselves. We have also identified metabolic regulators within breast cancer cells that may be targeted to reduce breast cancer metastases to the liver. Thus, this project will investigate the utility of targeting altered cancer cell metabolism as a means to impair metastasis.