Glucose and Lactate Transport in Pancreatic Cancer: Glycolytic Metabolism Revisited

Abstract

Membrane transporters fulfill essential roles in maintaining normal cellular function in health. In cancer, transporters likewise facilitate the aberrant characteristics typical of proliferating tumor cells. Pancreatic ductal adenocarcinoma is remarkable in its aggressiveness, and its metabolism is supported by a variety of membrane transporters. Glucose transporter 1 is upregulated in pancreatic cancer, enables rapid cellular uptake of glucose, and contributes to the invasiveness and metastatic ability of the disease. Likewise, the machinery of glycolysis, enzymes such as pyruvate kinase type M2 and hexokinase 2, is particularly active and ultimately leads to both lactate and tumor formation. Lactic acid channels and transporters include monocarboxylate transporters 1 and 4, connexin43, and CD147. In conjunction with glucose transporters and glycolytic metabolism, lactic acid transport helps perpetuate tumor cell metabolism and contributes to the formation of the unique tumor microenvironment in pancreatic cancer. These transporters may serve as potential therapeutic targets.