Abstract 1152: MUC1: A metabolic regulator in triple-negative breast cancer

Abstract

Abstract Breast cancer, the second leading cause of cancer deaths in women, is the most common cancer among North American women, accounting for nearly 1 in 3 cancer cases diagnosed in the U.S. women. Triple negative breast cancer (TNBC) subtype accounts for approximately 15-25% of all breast cancer cases and has an increased incidence of metastasis, high recurrence within 1-3 years and a high mortality rate. Therefore, identifying factors that facilitate tumor growth and metastases have the potential to serve as novel molecular targets for breast cancer therapy. Mucin1 (MUC1), a glycoprotein associated with chemoresistance, is aberrantly overexpressed in TNBC and facilitates growth and metastasis of TNBC cells. This occurrence can be partially attributed to MUC1 interaction with hypoxia-inducible factor alpha (HIF1α), a key regulator of glycolysis. As metastasis is the leading cause of cancer related deaths, this process relies on the ability of tumor cells to adapt to the changing nutrient levels in the surrounding stroma. In the present study we examined how signaling through MUC1 facilitates metabolic phenotype in TNBC; thus facilitating tumor growth and metastasis. Our results indicate that MUC1 expression facilitates glucose and glutamine uptake in a panel of TNBC cell lines. Furthermore, metabolomic analysis through liquid chromatography-coupled tandem mass spectrometry approach revealed that MUC1 expression modulates metabolite levels in glycolysis, pentose phosphate pathway and TCA cycle in TNBC cells. Thus, our results support the notion that MUC1 serves as a metabolic regulator in TNBC, facilitating metabolic reprogramming that influences growth of TNBC. Citation Format: Gennifer D. Goode, Nina Chaika, Vinee Purohit, Venugopal Gunda, Pankaj Singh. MUC1: A metabolic regulator in triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1152.