Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling.
Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling.
复制标题
亚牛磺酸通过异常的缺氧信号传导在神经胶质瘤中诱发恶性表型。
DOI：
10.18632/oncotarget.7710
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发表时间：
2016-03-22
期刊：
影响因子：
--
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Gao P;Yang C;Nesvick CL;Feldman MJ;Sizdahkhani S;Liu H;Chu H;Yang F;Tang L;Tian J;Zhao S;Li G;Heiss JD;Liu Y;Zhuang Z;Xu G
Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.
