Aerobic Glycolysis (the Warburg Effect)

The reprogramming of metabolism is now recognized to be a common feature of many cancer cells and the targeting of cancer metabolism pathways may offer potential therapeutic targets against a wide variety of cancer cells. The Warburg effect is the enhanced conversion of glucose to lactate observed in tumor cells, even in the presence normal levels of oxygen. Otto Heinrich Warburg demonstrated in 1924 that cancer cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well-oxygenated or not, a condition called aerobic glycolysis. Converting glucose to lactate, rather than metabolizing it through oxidative phosphorylation in the mitochondria, is far less efficient as less ATP is generated per unit of glucose metabolized. Therefore a high rate of glucose metabolism is required to meet increased energy needs to support rapid tumor progression.

Previously it was thought that the Warburg effect was a consequence of damage to the mitochondria or an adaptation to hypoxic conditions during the early avascular phase of tumor development. Current insight revealed that aerobic glycolysis supports various biosynthetic pathways and consequently the metabolic requirements for proliferation. The P13K pathway is considered to be a major determinant of the glycolytic phenotype through AKT1 and mTOR signaling and subsequent downstream HIF1 (Hypoxy Inducible Factor 1) (transcription factor) activation.

Another important pathway is the AMPK (AMP-activated protein kinase) pathway. AMPK is often considered as a metabolic checkpoint as it can control cell proliferation when activated under energetic stress. Mutations in tumor suppressor genes such as STK11 and LKB1, both involved in AMPK activation, have been identified in certain cancers and AMPK.

Sigma offers a wide selection of products for studying cancer metabolism, including many aerobic glycolysis inhibitors such as Dichloroacetic acid (DCA) and 2-deoxy-D-glucose (2DG).

1 Cairns, R.A., Harris, I.S., & Mak, T.W. Regulation of cancer cell metabolism. Nature Rev. Cancer, 11, 85-95 (2011).
2. Gatenby, R.A. & Gillies, R.J. Why do cancers have high aerobic glycolysis? Nature Rev. Cancer, 4, 891-899 (2004).
3. Vander Heiden, M.G., Cantley, L.C. & Thompson, C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324, 1029-1033 (2009)