Interleukin-1 beta Increases Glycolysis Through AKT and HIF-1 alpha in Colorectal Cancer Cells

Abstract

Increased glucose utilization and glycolysis is an important component in colorectal cancer. Inflammation is a known promoter of cancer development and progression. It has been reported that increased production of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) promote glycolysis. Previously, in colorectal cancer cells, we have demonstrated that IL-1β increased glycolysis, while suppressing oxidative metabolism. However, the mechanism underlying how this pro-inflammatory cytokine increased glycolysis was unclear. We hypothesized that IL-1β promoted glycolysis by increasing AKT activation given the metabolic role of this protein in metabolism. AKT is downstream of the interleukin-1 receptor, which is the major receptor IL-1β signals through to elicit a cellular response. Here, we show that upregulation of glycolysis by IL-1β is mediated through the AKT and more specifically the downstream transcription factor hypoxia inducible factor-1 alpha (HIF-1α). Knockout of HIF-1α completely abolished the elevated glycolysis induced by IL-1β. In addition, IL-1β had profound effects on mitochondrial function through reducing basal respiration, spare respiratory capacity, and maximal respiration. These data suggest a mechanism by which IL-1β through AKT activation and HIF-1α, regulates glycolysis in colorectal cancer cells. This work was supported by USDA NIFA (2019-67017-29261). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.