Project 466686

Breast cancer is the most common form of cancer among women and although treatment for breast cancer have progressed in recent years, many eventually become resistant to initial treatment. Therefore, there is a need to identify new targets for cancer treatment. Epithelial breast duct tissue is highly organized, and disruption of its organization is implicated in tumor progression. Ourlab recently identified that CD13, a membrane-bound protein, is required for lumen formation by directing apical membrane trafficking. Preliminary results from our lab reveal that loss of CD13 expression correlates with loss of cell polarity and tissue organization in breast cancer. With this project, we will determine if CD13 loss promotes tumor progression in breast cancer using primary mammary mouse cells where oncogene expression can be induced with doxycycline. We will knockdown CD13 and the impacts of this loss will be evaluated by measuring tumor size, determining proliferation, and evaluating polarity states of the organoids. The loss of CD13 will also be evaluated in a mouse model with similar experiments. It was additionally observed that CD13 expression is coupled with altered glutamine consumption. In many subtypes of breast cancer, glutamine metabolism is associated with more aggressive cancer and poorer outcome. Using the same cell type, the metabolic impact of CD13 loss will be further evaluated in normal and cancerous cells. We will determine if glutamine uptake is required for spheroid growth and we will monitor lumen formation with staining of different polarity proteins. Understanding how altered polarity and metabolism programs affects signaling in breast cancer is key to the identification of promising targets.