Role of sp transcription factors in the regulation of cancer cell metabolism

Abstract

Cancer cells exhibit altered metabolism characterized by the generation of adenosine triphosphate by glycolysis and generation of fatty acids by de novo synthesis. The majority of genes involved in these pathways have binding sites for specificity protein (Sp) transcription factors in their promoters. Studies showing that Sp transcription factors, particularly Sp1, are involved in the regulation in cancer cells of hexokinase, pyruvate kinase, lactate dehydrogenase, fatty acid synthase, and hypoxia-inducible factor-1α are reviewed. Glycolysis and lipogenesis in cancers are also known to be stimulated by the constitutive activation of the PI3K/Akt signaling pathway. Evidence is presented for the notion that Sp transcription factors may act in concert with Akt to regulate the abnormal metabolism of cancer cells.

Keywords: PI3K/Akt; Sp transcription factors; cancer cell metabolism; glycolysis; lipogenesis.

Figure 1.

Overview of glycolysis and lipogenesis pathways. Genes known to be regulated by Sp transcription factors are shown in bold; proteins known to be aberrant in cancer cells are italicized. *Aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase. ATP = adenosine triphosphate; CoA = co-enzyme A; TCA = tricarboxylic acid.