Differential phosphofructokinase-1 isoenzyme patterns associated with glycolytic efficiency in human breast cancer...

Cancers are characterized by an increasing glycolytic activity, which is called the Warburg effect. Although this phenomenon is well known, the mechanism of the enhanced rate of glycolysis in cancer has not yet been clearly recognized. The present study investigated the glycolytic rate, regulatory enzymatic activities and the expression of phosphofructokinase-1 (PFK-1) in human breast cancer and paracancer tissues. Human breast cancer tissues have an increased degree of glycolytic efficiency and regulatory enzymatic activities, which have been shown in previous studies. However, the present study identified a number of novel observations. The total PFK-1 levels were higher in human breast cancer tissues than in paracancer tissues, and further investigations revealed differential PFK-1 isoenzyme expression patterns between human breast cancer and paracancer tissues. The human breast cancer and paracancer tissues mainly expressed PFK-P and PFK-L isoforms, respectively. Linear-regression analysis showed that, depending on the pathological stage of breast cancer, the expression of PFK-P was significantly positively correlated with the activity of PFK-1. Thus, during the development of human breast cancer, the enhancement of glycolytic activity depends primarily on the conversion of the PFK-1, from PFK-L to PFK-P.