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Researchers Reveal the Roles of Polyamine Metabolism in Pathogenesis and Prognosis of Gastric Cancer


A study entitled "Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers" was published in Carcinogenesis by Prof. CHEn Yan’s group at Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences. This research reveals the unique roles of polyamine in the pathogenesis and prognosis of human gastric cancer.   

Polyamines plays numerous important roles for the proliferation and survival of the cells and an elevated polyamine level is required for the tumor cell transformation and tumor progression. Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in the biosynthesis of polyamines such as spermidine and spermine. While it is currently unknown whether AMD1 is implicated in the oncogenesis of gastric cancers.  

The study has provided evidence that AMD1 has a tumorigenic function in human gastric cancer cells via studies at the cellular, animal and human levels. At the cellular level, AMD1 has a positive effect on the proliferation and migration of human gastric cancer cells. At the animal level, AMD1 knockdown can strongly inhibit the growth of gastric cancer cells in vivo. Mechanistically, AMD1 regulates cell cycle progression by affecting G1-to-S transition. At the clinical level, AMD1 expression level was robustly upregulated in human gastric cancer samples in comparison with adjacent normal tissues.  

Besides, researchers found that AMD1 expression level is tightly associated with H. pylori 16sRNA, tumor size, tumor differentiation, tumor venous invasion, tumor lymphatic invasion, blood vessel invasion, invasive depth, and tumor stage. In addition, AMD1 protein is modulated by mTORC1 pathway in gastric cancer cells. This study uncovers the functional roles of polyamine metabolism in the tumorigenesis of human gastric cancers. 

This work was accomplished by Shanghai Institute of Nutrition and Health of Chinese Academy of Sciences and Zhejiang Cancer Research Institute. Dr. LING Zhiqiang from Zhejiang Cancer Research Institute is also the co-corresponding author of the publication. This study was sponsored by grants from the Ministry of Science and Technology of China, National Natural Science Foundation of China, Chinese Academy of Science, and Natural Science and Foundation of Zhejiang Province of China.