- The Warburg effect was an observation found in cancer cells by a German biochemist Otto Heinrich Warburg. He was able to observe that in cancer cells, there is a high rate of glycolysis under aerobic conditions, a trait which is technically inefficient for energy production in multicellular organisms. Hence due to his discovery, it subsequently also became known as the “Warburg Effect” over the years.
- Apparently Warburg was wrong. It was said in the paper that not all cancer cells have their mitochondria improperly functioning.
- In a proliferating cell, more than just requiring energy (ATP) for cell function, it also needs raw materials (nucleotides, amino acids and lipids) for duplicating organelles which is a needed step before undergoing cell division. So instead of utilizing most of the glucose present for mass energy production, the cancer cell has to also balance its resources between energy production and using it for organelle construction required in cell division. The Warburg effect may be inefficient in terms of energy production but this subsequent switch allows more glucose to be allocated for cell division.
- This is not necessarily true since some cells even before experiencing low oxygen conditions are already utilizing aerobic glycolysis. Examples noted in the paper are leukemic cells which are found in the blood stream- an area that has high oxygen concentrations and tumors located at our lung airways also exhibit the Warburg effect during tumorigenesis. This observation suggests that while hypoxic conditions do exist in cancer cells, it is late occurring and may not be an important factor causing the Warburg effect.
- PK-M2 is the only isoform of pyruvate kinase that can be controlled by tyrosine-phosphorylated proteins. Since tyrosine kinase which essentially activates or deactivates these control proteins, is an oncogene. Uncontrolled phosphotyrosine sending down growth signals in cancer cells decreases PK-M2 activity. This act in turn allows PK-M2 as the resource regulator in a cancer cell to prevent the full flow of glucose (its carbons) consumption for energy production and allows it to be redirected into biosynthetic pathways.
- In this paper, examples for cancer treatment are by primarily exploiting the cancer cell’s dependency to glucose which caused by the PI3K/Akt pathway, drugs that disrupt this pathway may affect glucose metabolism and effectively lead to cell death. Another possible way is by targeting key enzymes in glycolysis (PK-M2 and LDH-A) in which we try to control the cancer cell’s resource allocator enabling us to a degree regulate the cancer cell’s biosynthesis, and lastly by altering the amount of produced fuels from ingested food in a balance that less favors metabolic diseases that cancer related.
- It was hard at first since the paper is aesthetically intimidating to look at, especially during the initial skim and encountering “complicated” terms such as PK-M2, PI3K/Akt as well as a small font size and fitting a lot of words fitted into one page – this gave me fear and prejudice that this paper is out of my league and for “geniuses only” but after searching the difficult terms found within the paper, I got accustomed and it was downhill from there. So I started at 5 but went down to 2 as I was reading along. I had a lot of fun and learned a lot during reading this paper.
