Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin
Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin
复制标题
谷氨酰胺-果糖-6-磷酸转氨酶 2 (GFPT2) 通过激活己糖胺生物合成途径增加 β-连环蛋白的核位置来促进浆液性卵巢癌的 EMT
DOI：
10.1016/j.prp.2019.152681
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
令狐华
中科院分区：
文献类型：
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作者：
周琳;罗沐;程李娟;刘斌;令狐华
己糖胺生物合成途径（HBP）是葡萄糖代谢的一个分支，它为糖基化修饰提供底物，对细胞功能有广泛的影响。谷氨酰胺-果糖-6-磷酸转氨酶2（GFPT 2）是调节HBP的第一限速酶。鉴于GFPT 2表达与浆液性卵巢癌（SOC）患者的生存率呈负相关，我们试图研究GFPT 2在SOC中的作用及其相关机制。结果显示，GFPT 2在SOC组织中过表达，并且在90.SOC患者中观察到与晚期（FIGO III/IV）、次优切除率和较差生存率呈正相关。observed.in在GFPT 2敲低的SKOV 3和HEY细胞中，细胞迁移和侵袭也受到抑制。评价了O-连接的β-N-乙酰葡糖胺（O-GlcNAc）和核内β-连环蛋白的水平，并且观察到的由GFPT 2诱导的O-GlcNAc化的增加可能有助于上皮-间充质转化（EMT）。这些数据提供了对EMT中GFPT 2和O-GlcNAc酰化的功能的新的见解，从而提供了对侵袭性SOC的新的见解。
The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation.modification, which has a wide-ranging effect on cellular functions. Glutamine-fructose-6-phosphate.transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme. Given the.inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed.in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its.related mechanisms in SOC. The results showed that GFPT2 was over-expressed in SOC tissues, and positive.correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90.SOC patients. Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells. The.levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed.increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT). These .data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness .SOC.