PHGDH atypical metabolic activity regulates tumor mechanism revealed

Recently, the team of Professor Yuzheng Zhao from the School of Pharmacy of East China University of Science and Technology and the team of researcher Yuhui Jiang from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine have conducted an in-depth analysis of the nuclear translocation and enzymes of 3-phosphoglycerate dehydrogenase (PHGDH) under the condition of nutritional deficiency.
The molecular mechanism of biological transformation regulating nuclear NAD ⁺ and tumor cell growth
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Many studies have shown that metabolic enzyme expression levels, subcellular localization and changes in enzyme activity under different nutritional conditions can enable metabolic enzymes to regulate physiological activities such as cell signal transduction and gene expression in an accurate and effective manner
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Researchers have found that under normal or lack of glucose culture conditions, supplementation of exogenous serine to cells cannot effectively replenish the damage caused by PHGDH deficiency to cell growth, which indicates that PHGDH has a broader and unknown physiological role
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Aiming at the core metabolites of NAD(P)(H), etc.
, in recent years, Zhao Yuzheng and the team of Professor Yang Yi from Huali School of Pharmacy have developed a series of original, high-performance genetically encoded fluorescent probes, such as NADH probes.
SoNar/Frex, NAD ⁺ probe FiNad and NADPH probe iNap, etc.
, and established "high-throughput" and "panoramic" live cell metabolism monitoring and analysis methods, praised by international counterparts as "disruptive" technology, a series of research results Published 9 times in international authoritative academic journals
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In order to detect living cells the NAD ⁺ / NADH ratio and the NAD ⁺ levels, and researchers SoNar FiNad nucleus specific signal peptide probe labeling, in order to better explore the NAD ⁺ or NADH nuclear distributed in mammalian cells, they found In the absence of glucose, blocking the nuclear transport of PHGDH also leads to an increase in the level of NAD ⁺ in the nucleus
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In clinical pancreatic cancer samples, the phosphorylation levels of PHGDHSer371 and Ser55 were positively correlated with p38 and AMPK kinase activities, respectively
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This study clarified the molecular mechanism of PHGDH atypical metabolic activity regulating tumor growth, and explained the functional significance of changes in its enzyme activity in tumorigenesis, which will provide new ideas for the development of new tumor treatment strategies
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Related paper information: https://doi.