Abstract A45: Breast tumor metabolism

Abstract Proliferative cells have an increased need for macromolecular precursors required to sustain proliferation. Therefore, alteration of metabolic pathway flux and metabolite consumption is a hallmark of the transformed state. We have begun to investigate the specific metabolic pathway rewiring that occurs in the transformation of human breast cells, and the different metabolic phenotypes exhibited in breast cancers of specific molecular subtypes. These efforts have focused on the contribution of proper amino acid management in supporting breast tumor metabolism. For example, we have observed that ER-negative breast cancers exhibit activation of the serine biosynthetic pathway, controlled primarily by the expression of the enzyme PHGDH. ER-negative breast cancer cell lines with high PHGDH expression depend on its continued expression to maintain viability, and PHGDH expression permits cells to survive in the absence of extracellular serine. We have also identified the enzyme SHMT2, responsible for catabolizing serine for use in cellular methylation reactions, as an important determinant for cellular survival in low oxygen conditions. Finally, we have uncovered a key enzyme required to catabolize cysteine for the biosynthesis of iron-sulfur clusters, as being required for breast cancer cells to proliferate in high-oxygen environments, or under conditions of oxidative damage. We will discuss our development of mouse models to both investigate the contribution of these metabolic pathways to breast tumorigenesis and develop strategies to impact breast cancer growth and development. This work is supported by a Susan G. Komen Career Catalyst grant. Citation Format: Richard Possemato. Breast tumor metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A45.