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Unveiling the secret of tumor cells adapting stresses and providing a new therapeutic approach to treating cancers

Dr. Li-Mei Pai's laboratory at Chang Gung University has been using Drosophila and mammalian cells as model systems to study cell physiology. Recently, Dr. Pai together with Dr. Wei-Cheng Lin and her lab members, the Proteomics, Metabolomics and Bioinformatics Core Laboratories found that cancer cells formed CTP synthase (CTPS) filaments in nutrition-deficient conditions to facilitate the adaptation of stressed environment to maintain their growth advantage. The team is the first to discover that histidine, an essential amino acid, is the main player for CTPS filament formation. The new discovery may open a new avenue in cancer research filed was published in “Cell Reports”.

The enzymatic activity of CTPS is critical for the growth of cancer cells, however, when overgrowing the supply of nutrition is not enough to the meet the demand of the abnormal cells, resulting in stressed conditions and, thus, developing adaptation. After analyzing The Cancer Genome Atlas (TCGA) database, the team found that cancer cells are capable of regulating histidine metabolism to facilitate the filament formation by inhibiting CTPS enzymatic activity and reducing energy consumption to overcome the adverse environment. In addition, histidine metabolism contributes to protein methylation to regulate cell physiology. The study sets out details on how cells develop favorable conditions against stress by reprograming their metabolic pathways. This study may provide new strategies and opportunities for treating cancers.

The team led by Dr. Pai will continue to collaborate with the Core Laboratories at Chang Gung University to study how histidine affects the physiology of cancer cells, which may pave the way to novel cancer treatments.
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