FOXK1 and its closely relate siblingFOXK2 induce aerobicglycolysis by upregulating the enzymatic machinery required for this (for example,hexokinase-2,phosphofructokinase,pyruvate kinase, andlactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in themitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit ofpyruvate dehydrogenase phosphatase 1 this leads to increasedphosphorylation of the E1α regulatory subunit of thepyruvate dehydrogenase complex, which in turn inhibits further oxidation ofpyruvate in the mitochondria—instead,pyruvate is reduced tolactate. Suppression of FOXK1 and FOXK2 induce the oppositephenotype. Bothin vitro andin vivo experiments, including studies of primary human cells, show how FOXK1 and/or FOXK2 are likely to act as important regulators that reprogram cellular metabolism to induce aerobic glycolysis.[7]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Katoh M, Katoh M (July 2004). "Identification and characterization of human FOXK1 gene in silico".International Journal of Molecular Medicine.14 (1):127–132.doi:10.3892/ijmm.14.1.127.PMID15202027.
Huang JT, Lee V (September 2004). "Identification and characterization of a novel human FOXK1 gene in silico".International Journal of Oncology.25 (3):751–757.doi:10.3892/ijo.25.3.751.PMID15289879.