Abstract 1446: Glycogen accumulation in aggressive breast cancers under hypoxia

Abstract

Abstract Cancers utilize diverse metabolic pathways to increase survival and proliferation; therefore, the identification of specific metabolic alterations in aggressive triple-negative and inflammatory breast cancers is a compelling avenue for the development of new treatments. The ability to survive and grow in hypoxia is necessary for breast cancer cells in the center of the tumor mass or in the lymphatic system and other organ environments. Glucose reserves are typically stored in liver and muscle cells as the polysaccharide glycogen. Elevated levels of glycogen have been observed in various cancers, and recent studies have suggested that glycogen metabolism is important for promoting cancer cell survival. We hypothesize that aggressive breast cancers modulate glycogen metabolism to provide nutritional flexibility for proliferation and invasion during cancer progression. To test our hypothesis, we investigated the regulation of glycogen levels in breast cancer and normal-like cells in atmospheric and 1% oxygen. The glycogen content of six breast cancer and one normal-like cell line was measured under normoxic and hypoxic conditions. All cell lines had increased glycogen accumulation under hypoxia, but to varying degrees that did not correlate with receptor status. Expression levels of various genes involved in glycogen synthesis and degradation were determined by qRT-PCR, with no consensus expression pattern between all cell lines. Several key alterations were noted in synthesis and degradation enzymes. We will present an integrative picture of glycogen synthesis and degradation in breast cancer cells. Studies are ongoing to determine the mechanisms through which these changes occur and whether the accumulation of glycogen confers an advantage for continued survival and growth of cancer. Citation Format: Megan Ann Altemus, Joel A. Yates, ZhiFen Wu, LiWei Bao, Sofia D. Merajver. Glycogen accumulation in aggressive breast cancers under hypoxia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1446.