A novel Mechanism of Cancer Cells Adaptation to Sugar Deprivation discovered

Glucose is a sugar that is essential for the body's energy balance and the most important source of energy for the brain and muscles. If glucose is lacking, this creates considerable stress to the cells of the body. This is especially true for cancer cells, which have a high demand for glucose. However, due to a deficient vascular supply of the tumor tissues, cancer cells live under a permanent state of glucose deprivation. This forces cancer cells to adapt their metabolism.  Researchers have now uncovered how this happens: a mechanism that can be traced back to baker's yeast is the key. This mechanism can be blocked and can thus lead to the death of tumor cells. Using the example of malignant brain tumors, a research team co-led by Dr. Gabriel Leprivier (University Hospital Düsseldorf, Germany) and Dr. Barak Rotblat (Ben Gurion University, Israel) is reporting this fundamental mechanism in the journal Nature Communications.

How do cancer cells adapt to glucose deficiency and how does this adaptation lead to more aggressive tumors that are more difficult to treat? By studying the behavior of normal cells, the scientists discovered that cancer cells hijack the natural metabolic response to glucose deficiency. When cells are supplied with sufficient glucose, we all know that it is used to produce fat. Thus, when glucose is missing, cells stop making fat. The researchers have now identified the molecular switch that allows cells to stop producing fat when sugar is lacking - the protein 4EBP1. Remarkably, if this molecular switch is blocked, cells will continue to make fat even in absence of any sugar, which will exhaust cells and ultimately lead to cell death.

In patients with an aggressive brain tumor called glioblastoma, the protein 4EBP1 is very active. Studies using animal models have shown that blocking 4EBP1 can inhibit the growth of these brain tumors. This may open up the possibility that the 4EBP1-mediated metabolic switch could represent a novel therapeutic target for the treatment of malignant brain tumors.