Why do some anti-glutamine therapies fail? A new study uncovers a hidden metabolic workaround involving pyruvate, biotin, and mutations in the FBXW7 gene.
Scientists at the University of Lausanne have uncovered a cellular mechanism that reveals a hidden weakness in tumor cells when they are deprived of vitamin B7.
All living cells must constantly adjust to changes in nutrient supply. This flexibility is essential for survival. However, some cells develop a strong reliance on glutamine, an amino acid that plays a central role in metabolism. Glutamine supplies critical components needed to build proteins and DNA. When it is unavailable, cells are unable to continue dividing.
Cancer cells are a prime example. Their reliance on this nutrient, often described as “glutamine addiction,” is considered a well-known weakness. Even so, many tumors find ways to overcome this dependence. In research published in the journal Molecular Cell, a team led by Alexis Jourdain, assistant professor in the Department of Immunobiology (DIB) at Unil’s Faculty of Biology and Medicine (FBM), clarifies biological processes that were not fully understood until now.
How Cells Bypass Glutamine Dependence
The study was spearheaded by Dr. Miriam Lisci, a postdoctoral researcher in Prof. Jourdain’s lab. The researchers focused on carbon-rich molecules, especially pyruvate, and found that these compounds allow cells to keep dividing even when glutamine levels are low.
Their experiments showed that this workaround depends on a mitochondrial enzyme known as pyruvate carboxylase. For this enzyme to operate, it must bind to vitamin B7 (or biotin). Without vitamin B7, the enzyme remains inactive, and cell growth comes to a halt.
