Scientists at the University of Lausanne have identified a biological process that reveals a key weakness in tumor cells lacking vitamin B7.
Cells adapt to fluctuations in nutrient availability to endure. Yet, certain cells grow highly dependent on glutamine, an amino acid vital for metabolism. It supplies building blocks for proteins and DNA, and without it, cells fail to proliferate.
Tumors often display this ‘glutamine addiction,’ relying extensively on the nutrient. While seen as a potential target, many cancers adapt around it. In research published in Molecular Cell, a group headed by Alexis Jourdain, an assistant professor in the Department of Immunobiology at the university’s Faculty of Biology and Medicine, explores the mechanisms enabling this flexibility.
Role of Pyruvate and Vitamin B7 in Cell Proliferation
The work, directed by postdoctoral researcher Miriam Lisci in Jourdain’s group, examined carbon-containing compounds like pyruvate. These can enable cells to continue dividing despite low glutamine levels.
The team discovered that this relies on a mitochondrial enzyme known as pyruvate carboxylase, which needs vitamin B7 (biotin) to operate. Without the vitamin, the enzyme ceases function, halting cell expansion. Thus, biotin serves as a metabolic enabler, permitting pyruvate to support the cell’s energy needs and offset glutamine shortages.
Impact of FBXW7 Mutations on Cancer Susceptibility
The investigation also highlighted a novel function for the FBXW7 gene, commonly associated with malignancies. ‘Mutations in FBXW7, common in some cancers, lead to partial loss of pyruvate carboxylase, reducing pyruvate efficiency and heightening glutamine reliance,’ said Miriam Lisci, the paper’s lead author.
Researchers showed that particular FBXW7 mutations observed in patients directly cause this elevated glutamine dependence. These insights stemmed from partnerships with the faculty’s metabolomics and proteomics facilities, plus Owen Skinner’s group at Northeastern University in the US.
Explaining Treatment Shortcomings and Future Directions
These results clarify why interventions targeting glutamine sometimes fall short, as tumors shift to other metabolic routes for survival.
‘Over time, this work paves the way for deeper insights into cancer’s metabolic weaknesses and for developing advanced treatments that address tumors’ metabolic adaptability, such as by attacking multiple pathways at once,’ noted Alexis Jourdain, the study’s senior author.
