The Warburg Effect
We know that although cancer cells are derived from our own healthy cells, they undergo many changes that render them distinctive from normal cells. In the 1950s, a scientist named Otto Warburg discovered quite a startling difference in the metabolism between tumor cells and normal cells. This difference, now called the Warburg Effect, describes how cancer cells obtain energy. The Warburg Effect is most often learned in college biology or molecular biology classes, and it’s a subtle concept. Let’s go over it here, starting with a refresher on cellular respiration.
What is cell respiration?
Cells derive energy from glucose through a process called respiration. Respiration can be aerobic (with oxygen) or anaerobic (without oxygen). Aerobic respiration requires oxidative phosphorylation in the mitochondria and produces 36 mols of ATP per mol of glucose and CO2 as a byproduct. Anaerobic respiration metabolizes glucose to lactate and produces 2 mols of ATP per mol of glucose. Human cells can (and do) undergo both forms but since aerobic respiration results in such a greater energy yield, if oxygen is present, it is the preferred mechanism.
In cancer cells, an interesting phenomenon exists. Cancer cells, even in the presence of oxygen, will preferentially metabolize the majority of glucose through anaerobic fermentation instead of aerobic respiration. This is the Warburg Effect, and you can see why scientists found it startling when it was first discovered: the cancer cells seem to have chosen a metabolism that gives them less energy, which is very counterintuitive!
Why could this be? What is driving this change?
As a biology tutor, I urge my students to always be thinking about pathways and processes: if something goes wrong in one place how can it affect the cell in an empirical way, a way we could measure in a lab?
One hypothesis proposed to explain the Warburg effect was that cancer cells have defective mitochondria. However, several subsequent studies found that wasn’t likely. Another suggestion is that tumors live densely packed together in an in-vivo (within the body), naturally hypoxic (lower oxygen concentration) environment. The lack of oxygen would induce cells to switch to anaerobic respiration. However, that doesn’t explain why such cells in vitro (out of the body) still exhibit the Warburg Effect. Other theories consider how switching respiration pathways could convey a competitive advantage to the cell (always be considering that when you see biology questions too!). One theory suggests that the TCA cycle in aerobic respiration is being used in other capacities, like for example, synthesizing biomaterials for a rapidly dividing tumor cell. In this way, the cell has chosen to produce less energy in return for being able to produce more biomass.
The Warburg Effect, although now documented for over 80 years, is a topic that scientists are still investigating. If we can understand how cancer cells get energy and divide, we can design targeted drugs to attack them.
References
- Vander Heiden, M.G.; Cantley, L.C.; and Thompson, C. B. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science. 2009, 324, 1029-1033
- Nakashima R.A.; Paggi M.G.; & Pedersen P.L. Contributions of Glycolysis and Oxidative Phosphorylation to Adenosine 5’-triphosphate Production in AS-30D Hepatoma cells. Cancer Res, 1984, 44:5702-5706.
- Moreno-Sanchez, R.; Rodriguez-Enriquez S.; Marin-Hernandez; Saaverdra E. Energy Metabolism in Cancer Cells. FEBS Journal, 2007, 274: 1393-1418.
Comments