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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a horrible disease with a five-year survival of 8% [1]
There are two opposing explanations accounting for the high expression of Glucose transporters (GLUTs)-1 that illustrate its role in hypoxic and oncogenic pathways: (1) glucose is used in excess via glycolytic pathways leading to intracellular depletion of glucose and the subsequent recruitment of facilitative transport enables a sustained high metabolic rate, and (2) the increased expression of GLUT-1 allows accelerated glycolysis by increasing intracellular glucose concentrations beyond normal physiological limits
Transporters play a facilitative role in the metabolism that characterizes PDAC tumor cells
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a horrible disease with a five-year survival of 8% [1]. One familiar observation in many cancers, including PDAC, is a profound reprogramming of cellular metabolism. When this reprogramming involves a transition to aerobic glycolysis, it is commonly referred to as the Warburg effect. Tumors exhibiting the Warburg effect do not fully oxidize glucose to its potential. This review focuses on the metabolite transporters that are active in PDAC, namely, the conduits of glucose and lactic acid. Their roles in facilitating abnormal metabolism, formation of the tumor microenvironment, and possible therapeutic implications are discussed
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