Functions of Key Enzymes of Glycolytic Metabolism in Tumor Microenvironment

The tumor microenvironment (TME) plays a crucial role in tumor initiation, growth and metastasis. Metabolic enzymes involved in tumor glycolytic reprogramming, including hexokinase, pyruvate kinase, and lactate dehydrogenase, not only play key roles in tumorigenesis and maintaining tumor cell survival, but also take part in the modulation of the TME. Many studies have been devoted to the role of key glycolytic enzymes in the TME over the past decades. We summarize the studies on the role of glycolytic enzymes in the TME of these years and found that glycolytic enzymes remodel the TME primarily through regulating immune escape, angiogenesis, and affecting stromal cells and exosomes. Notably, abnormal tumor vascular system, peritumoral stromal cells, and tumor immunosuppressive microenvironment are important contributors to the failure of antitumor therapy. Therefore, we discuss the mechanisms of regulation by key glycolytic enzymes that may contribute to a promising biomarker for therapeutic intervention. We argue that targeting key glycolytic enzymes in combination with antiprogrammed cell death ligand 1 or antivascular endothelial growth factor could emerge as the more integrated and comprehensive antitumor treatment strategy.