The bifunctional 6-phosphofructo-2-kinase (EC18.104.22.168)/fructose-2,6-bisphosphatase (EC22.214.171.124) (PFKFB) regulates the steady-state concentration of fructose 2,6-bisphosphate, an activator of a key regulatory enzyme of glycolysis, phosphofructokinase.
Latest research made by scientists at Cancer Research UK’s London Research Institute show that an enzyme called PFKFB4 is essential for balancing these two processes – making sure the cell’s energy needs are met without allowing free radicals to build up and trigger cell death. Study leader Dr. Almut Schulze, said: “Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. Blocking this enzyme in prostate cancer cells grown in the lab stalled growth and triggered a catastrophic build-up of free-radicals, suggesting that it could be a suitable drug target. Importantly, this route to energy production is common to many different types of cancer, suggesting that drugs to target it could potentially be used to treat a variety of cancers.”
^Manzano A, Pérez JX, Nadal M, Estivill X, Lange A, Bartrons R (March 1999). "Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene". Gene229 (1-2): 83–9. doi:10.1016/S0378-1119(99)00037-2. PMID10095107.
Minchenko OH, Ochiai A, Opentanova IL, et al. (2005). "Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors.". Biochimie87 (11): 1005–10. doi:10.1016/j.biochi.2005.04.007. PMID15925437.
Minchenko O, Opentanova I, Minchenko D, et al. (2004). "Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation.". FEBS Lett.576 (1-2): 14–20. doi:10.1016/j.febslet.2004.08.053. PMID15474002.
Bobarykina AY, Minchenko DO, Opentanova IL, et al. (2006). "Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers.". Acta Biochim. Pol.53 (4): 789–99. PMID17143338.
Susana Ros, Claudio R. Santos, Sofia Moco, Franziska Baenke, Gavin Kelly, Michael Howell, Nicola Zamboni, Almut Schulze; et al. "Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival.". Cancer Discovery.