Cancer cells need a lot of energy to grow fast—to do so, they show abnormal metabolic pathways.
Most mammalian cells use glucose as a fuel source. Glucose is metabolized by glycolysis in a multistep set of reactions, resulting in the creation of pyruvate. In typical cells under normal oxygen levels, much of this pyruvate enters the mitochondria, where it is oxidized by the Krebs Cycle to generate ATP to meet the cell’s energy demands.
However, in cancer cells or other highly proliferative cell types, much of the pyruvate from glycolysis is directed away from the mitochondria to create lactate through the action of lactate dehydrogenase (LDH/LDHA)—a process typically reserved for the low oxygen state. In contrast to mitochondrial glycolysis, lactate production in the presence of oxygen is termed “aerobic glycolysis” or the Warburg Effect. Several signaling pathways contribute to the Warburg Effect and other metabolic phenotypes of cancer cells. If you look at the pathway, you might notice PI3K/Akt, mTOR, Erk1/2 MAPK, ULK1 (Autophagy), p53, HIF1alpha, (Hypoxia – Angiogenesis), and AMPK all represented.
Cancer cells frequently use glutamine as another fuel source, which enters the mitochondria and can be used to replenish Krebs Cycle intermediates or to produce more pyruvate through the action of malic enzyme, or to produce building blocks to help the increased cell growth.
Cancer cells can become addicted to glutamine, with glutamine itself promoting cell proliferation. For this reason, glutamine metabolism is becoming a hot research area for cancer researchers. Because glycolysis is an intricate process, influenced by so many factors, there are many pathways to research. Check out some of these signaling players today.
The Hallmarks of Cancer were identified by Weinberg and Hanahan and were originally published in Cell1. The authors propose the idea that the complexity of cancer can be broken down to smaller subsets of underlying principles. The information here pertains to one such subset. Other entries in this series explore the other known Hallmarks.
1 Hanahan D, Weinberg RA (January 2000). "The Hallmarks of Cancer". Cell. 100 (1): 57– 70. doi:10.1016/S0092-8674(00)81683-9