The main energy currency of cells is ATP and one might expect that not only contracting muscle, but also uncontrollably dividing cancer cells would have a high demand for ATP. However, for some reason cancer cells have re-programmed their metabolic engines to produce less ATP. The phenomenon, known as Warburg effect, is typical for cancer cells and the mechanism behind is believed to benefit cancer cells by switching biochemical engines from energy manufacturing reactions to anabolic reactions, which primarily support growth of the cell size and proliferation.
The triggers for "non-stop" proliferation programs in cancer cells are the tumor-promoting oncoproteins, like protein called Myc. Luckily, it seems that oncoproteins are not perfect programmers.
Finnish scientists from the University of Helsinki, investigating how Myc re-engineers metabolic pathways in cells, have identified an unexpected branch in the pathway - a branch that ends to cell death (apoptosis).
The researchers found that Myc activates cancer-like changes in cell metabolism, causing a sudden fall in ATP concentration inside the cells. Declining ATP levels awake a bioenergy sensor protein known as AMP kinase (AMPK), which starts a biochemical chain of events moving a tumor suppressor protein p53 to the surface of the mitochondria. At mitochondria, p53 activates apoptosis-promoting proteins, the investigation suggests.
According to University of Helsinki scientist and Finnish Academy Research Fellow Juha Klefström, PhD, who led the study, "Myc oncoprotein not only boosts tumor cell proliferation but it also makes the cells vulnerable to cell suicide program, apoptosis. The cancer gene dependent vulnerability to apoptosis has promise to be the prime target for future targeted cancer therapies but first, we need to understand the cell pathways that are causing this vulnerability. The investigated connections between Myc, energy metabolism and apoptosis will help us to understand the biochemistry of cancer cell apoptosis. However, the finding is also interesting from a therapeutic standpoint since there are many drug-like molecules that can be used to turn on and off the AMPK controlled pathways in cancer cells."
Healthy cells may encounter ATP and energy shortage for example, during strenuous exercise, so that alone is not sufficient to kill the cells. Why then Myc oncoprotein transformed cells succumb to ATP deprivation?
Advertisement
How can these cancer cell specific metabolic pathways and reactions be targeted with drugs?
Advertisement
The study will be published in the Proceedings of the National Academy of Sciences (PNAS) Online Early Edition on the 15th April, 2013.
Source-Eurekalert