The role of 6-phosphofructo-2-kinase (PFK-2)/fructose 2,6-bisphosphatase (FBPase-2) in metabolic reprogramming of cancer cells

• Main Authors: Kinga A. Kocemba, Joanna Dulińska-Litewka, Karolina L. Wojdyła, Przemysław A. Pękala
• Format: Article
• Language: English
• Published: Index Copernicus International S.A. 2016-09-01
• Series: Postępy Higieny i Medycyny Doświadczalnej
• Subjects: PFKFB3; PFKFB4; fosfofruktokinaza II; glikoliza; efekt Warburga; Glycolysis
• Online Access: http://phmd.pl/gicid/01.3001.0009.6872
• ISSN: 0032-5449; 1732-2693

The high rate of glucose breakdown is the fingerprint of cancer. Increased glycolysis allows tumour cells to fulfil their high energetic and biosynthetic demands. Interestingly, however, rather than metabolizing glucose in the oxidative phosphorylation pathway, cancer cells generally use glucose for aerobic glycolysis. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental forms of metabolic reprogramming during cancerogenesis. Changes in the rate of glycolytic activity of cancer cells are caused mainly by the increased expression of glycolytic enzymes as a consequence of activation of oncogenes or loss of tumour suppressors. In addition, the hypoxic tumour environment also triggers upregulation of a series of genes involved in glucose metabolism. Among the metabolic enzymes that are modulated by these factors in cancer cells are the 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatases (PFKFBs), a family of bifunctional enzymes that control the levels of fructose 2,6-bisphosphate (Fru-2,6-P2), an essential activator of the glycolytic flux. Fru-2,6-P2 strongly activates glucose breakdown in glycolysis through allosteric modulation of the rate-limiting enzyme of glycolysis, phosphofructokinase-1 (PFK-1). Thus far, many studies have reported a correlation between aberrant PFKFB expression level and the grade of tumour aggressiveness, which directly indicates that these enzymes may play a crucial role in cancerogenesis. The objective of this review is to highlight the recent studies on aberrant expression of PFKFBs and its influence on cancer progression.