On April 3, 2018, Nature published an online article called Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. The article points out that the Warburg pathway enzyme PFKFB4 acts as a molecular fulcrum that couples sugar metabolism to transcriptional activation by stimulating SRC-3 to promote aggressive metastatic tumours.

PFKFB4 also known as 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 which in humans is encoded by the PFKFB4 gene is an activator of a key regulatory enzyme of glycolysis and phosphofructokinase. PFKFB4 is a bifunctional enzyme that can increase intracellular F2,6BP and, thus, flux through PFK-1 or decrease F2,6BP and PFK-1 activity resulting in increased shunting of glucose 6-phosphate for NADPH and ribose production. PFKFB4 was observed to be over-expressed in human tumors indicating a potential role in cancer development and/or progression. This protein is highly expressed in cancer cells and is induced by hypoxia and is essential to the survival of cancer cells under conditions of hypoxia. This suggests that PFKFB4 may be a useful molecular target for the development of anti-neoplastic agents. 

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