Abstract 1838: MUC1 serves as 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. In the present study we examined the effect of MUC1 expression on cancer cell metabolism of TNBC cell lines under normoxic (20% Oxygen) and hypoxic (1% Oxygen) conditions. MUC1 was ectopically overexpressed in the MDA-MB-231 cell line and stably knocked down in the MDA-MB-468 cell line. Results indicate that MUC1 interacts with HIF1α and the interaction is further enhanced under hypoxic conditions. In addition, MUC1 expression enhanced glucose and glutamine uptake, enhanced lactate secretion and altered the expression of several metabolic genes. Furthermore, untargeted global metabolomic profiling identified metabolite alterations in which MUC1 expression modulates cancer cell metabolism to facilitate growth properties of 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. MUC1 serves as metabolic regulator in triple negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1838. doi:10.1158/1538-7445.AM2015-1838