Researchers at the University of Lausanne (Unil) have discovered a new biological mechanism by which vitamin B7 deficiency exposes critical vulnerabilities in tumor cells.
すべての細胞は、生き残るために栄養供給の変化に適応する必要があります。 However, some cells become particularly dependent on glutamine, an amino acid that plays a major role in metabolism. Glutamine provides an essential component needed for the construction of proteins and DNA, and without it cells cannot continue to grow and divide.
Cancer cells are a typical example. Many tumors exhibit what scientists call “glutamine toxicity,” meaning they are highly dependent on this nutrient.この依存性は弱点と考えられていますが、多くのがんはそれを回避する方法を見つけています。 In a study published in a journal molecular cellA team led by Alexis Jourdain, assistant professor in the Department of Immunobiology (DIB) at the University of Biology and Medicine (FBM), has shed new light on the cellular processes behind this adaptability.
The study, led by Dr. Miriam Lissi, a postdoctoral researcher in Professor Jordain’s lab, focused on carbon-rich molecules, specifically pyruvate.これらの分子は、グルタミンが不足している場合でも細胞が分裂し続けることを可能にします。
The research team discovered that this process relies on a mitochondrial enzyme called pyruvate carboxylase.この酵素が機能するにはビタミン B7 (またはビオチン) が必要です。ビタミンB7が利用できない場合、酵素は機能を停止し、細胞の成長が停止します。 In this way, biotin acts as a “metabolic license”, allowing pyruvate to be supplied to the cell’s energy system and compensate for the lack of glutamine.
FBXW7 gene mutation increases cancer vulnerability
FBXW7a gene frequently associated with cancer. “when FBXW7 “There is a partial loss of pyruvate carboxylase, a situation that frequently occurs in some cancers, and pyruvate cannot be used efficiently, making cells dependent on glutamine,” explains Miriam Lisci, first author of the paper.
Researchers have demonstrated something concrete. FBXW7 患者で見つかった突然変異は、グルタミンへの依存度の増加を直接引き起こす可能性があります。 These discoveries were made possible through FBM’s metabolomics and proteomics platform and collaboration with Professor Owen Skinner’s team at Northeastern University, USA.
The findings also help explain why treatments aimed at blocking glutamine are not always successful.がん細胞は生き残るために別の代謝経路に切り替えることができます。
“In the long term, this study opens new avenues to better understand the metabolic vulnerabilities of cancer, especially by targeting multiple metabolic pathways simultaneously, and to design innovative therapeutic strategies that take into account the great metabolic flexibility of tumor cells,” concluded Alexis Jourdain, the study’s senior author.
