Metabolic and tumorigenic consequences of glycogen synthase knockout in prostate cancer cells

Abstract

Glycogen Synthase is the key enzyme in glycogen metabolism that catalyzes the polymerization of glycogen chain. With the emergence of evidence suggesting its involvement in cellular regulatory pathways, its roles in metabolism recently have been investigated in various studies. As yet, its importance in the growth and development of cancer cells is still largely unknown. In the present study, the metabolic and tumorigenic consequences of glycogen synthase knockout in prostate cancer cells is the area of interest. To examine the possible role played by glycogen synthase in protecting or sensitizing cancer cells towards stress, the Glycogen Synthase 1 gene in the human prostate cancer cell line (22Rv1) is previously modified with CRISPR-Cas9 to abolish the synthesis of glycogen synthase in these cells. Under two separate conditions of glucose deprivation and addition of the mitochondrial inhibitor oligomycin, the modified 22Rv1 cells showed obvious increase in cell apoptosis as measured by Western Blotting and flow cytometry. Meanwhile, xenografts that were obtained by injection of modified 22Rv1 cells into mice were found to exhibit a significantly increase in tumor size and apoptosis marker that differed from those obtained with normal 22Rv1 cells. The results of this study suggested that the lack of glycogen synthase expression promotes apoptosis of 22Rv1 cancer cells under in vitro stress conditions. Such a role of glycogen synthase may also be essential to the control of growth and development of tumor in vivo. Our results are in line with the recent notion that the function of glycogen synthase may not be restricted to its role in glycogen metabolism, especially in cancer cells. However, the exact mechanism by which glycogen synthase is related to cell survival under stress conditions will require further study.