The Warburg Effect

You have been reading a lot on the RNA world: from riboswitches to aptamer biosensors designed by methods such as SELEX. Today, we talk about the metabolism portion of our consortium, and specifically a metabolic phenomenon that cancer cells undergo, known as the Warburg Effect.

One of the defining differences between unicellular organisms, such as bacteria, and multi-cellular organisms, such as human beings, is that unicellular organisms are evolutionarily driven to divide and reproduce as quickly as possible under conditions of excess nutrition. When nutrients are scarce, they stop the production of biomass and change their metabolic activity to cope with conditions of starvation.

You could think of unicellular organisms as an anarchy, where every man is for himself. In contrast, a multi-cellular organism is an intricate bureaucratic network, where each cell is given a singular task that it must accomplish and several control systems are in place to dissuade aberrant individual cell proliferation, even when nutrient availability exceeds the levels at which cell division is supported. Cancer occurs when cells overcome the control of the systems in place; that is, they no longer respond, properly, to the expression of growth factors due to acquisition of genetic mutations that alter the signalling pathways that cells use to communicate with each other and their environment.

The expression of these genes, known as oncogenes, also lead to an altered metabolism in cancer cells as compared to normal cells. Indeed, one of the best-known metabolic abnormality in cancer cells is the Warburg Effect, first introduced by the German physiologist, Otto Warburg, who received the Nobel Prize in Physiology for this discovery in 1931.

The difference in metabolism in normal (left) vs. cancer (right) cells due to the Warburg effect.

The Warburg Effect shows that one of the prime differences in normal versus cancer cells is that when there is oxygen availability, normal cells go through what is known as aerobic respiration. That is, most of their cellular energy, or adenosine triphosphate (ATP), comes from oxidative phosphorylation. In this process, pyruvate, a product of glycolysis, enters the mitochondria, also known as the powerhouse of the cell, and goes through the tricarboxylic acid (TCA) cycle to help run the electron transport system. The Warburg Effect states that cancer cells go through aerobic glycolysis, meaning that they consume much more glucose to produce most of their cellular energy, or ATP, through glycolysis and instead of using the pyruvate in the TCA cycle, they convert it to lactic acid.   

Since the discovery of the Warburg effect, we have learned that tumor-related metabolic alterations are not limited to the balance between glycolytic fermentation and oxidative phosphorylation. There are key tumor genes, such as p53 and Myc that regulate metabolism in cancer cells in a much more complex manner.  

The Warburg Effect is an important example of the value in understanding the links between cellular metabolism and growth control for better treatments to human cancer.

Further reading:
Otto Warburg. On the Origin of Cancer Cells. Science (1956).


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