Glycogen metabolism is dispensable for tumor progression in clear cell renal cell carcinoma

Glycogen accumulation is a highly consistent, distinguishable characteristic of clear cell renal cell carcinoma (ccRCC)(1). While elevated glycogen pools might be advantageous for ccRCC cells in nutrient deprived microenvironments to sustain tumor viability, data supporting a biological role for glycogen in ccRCC are lacking. Here, we demonstrate that glycogen metabolism is not required for ccRCC proliferation in vitro nor xenograft tumor growth in vivo. Disruption of glycogen synthesis by CRISPR-mediated knockout of glycogen synthase 1 (GYS1) has no effect on proliferation in multiple cell lines, regardless of glucose concentrations or oxygen levels. Similarly, prevention of glycogen breakdown by deletion or pharmacological inhibition of glycogen phosphorylases B and L (PYGB and PYGL) has no impact on cell viability under any condition tested. Lastly, in vivo xenograft experiments using the ccRCC cell line, UMRC2, reveal no significant alteration in tumor size or volume when glycogen metabolism is altered, largely phenocopying our in vitro observations. Our findings suggest glycogen buildup in established ccRCC tumor cells is likely to be a secondary, and apparently dispensable, consequence of constitutively active HIF-1α signaling.