GLUT5 increases fructose utilization and promotes tumor progression in glioma
GLUT5 increases fructose utilization and promotes tumor progression in glioma
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DOI：
10.1016/j.bbrc.2018.04.103
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发表时间：
2018-06-02
影响因子：
3.1
通讯作者：
Gao, Wenbo
中科院分区：
文献类型：
--
作者：
Su, Chunhai;Li, Hui;Gao, Wenbo
果糖现在是人类饮食中如此重要的成分，一些研究发现一些癌细胞可以利用果糖来克服低糖的微环境，但关于果糖在胶质瘤中的作用的研究很少。为了探讨果糖在胶质瘤中的作用，我们检测了胶质瘤细胞在果糖中的增殖和集落形成能力，发现胶质瘤细胞在果糖中的增殖和集落形成能力与在葡萄糖中的能力相似，但果糖只能部分恢复正常胶质细胞的增殖能力。为了探讨其机制，我们比较了GLUT5(葡萄糖转运体5)在这些细胞系中的表达水平，结果表明，胶质瘤细胞系的GLUT5表达高于正常胶质细胞系。在果糖条件下，GLUT5基因敲除可显著抑制胶质瘤细胞的增殖。此外，我们还发现GLUT5在胶质瘤组织中也有较高的表达，并且GLUT5的表达与胶质瘤的恶性程度和患者的生存不良显著相关(p<；0.01)。此外，我们还发现GLUT5基因的敲除在体内可以显著抑制肿瘤的增殖，摄入果糖可以显著增加肿瘤的体积。综上所述，我们的数据表明，果糖可以被胶质瘤细胞利用，限制果糖摄取或靶向GLUT5可能是治疗胶质瘤的有效策略。(C)2018 Elsevier Inc.保留所有权利。
Fructose is now such an important component of human diets, and several studies have found that some cancer cells could utilize fructose to overcome low glucose micro-environment, but the study on the role of fructose in glioma is rare. To explore the role of fructose in glioma, we detected the proliferation and colony formation ability of glioma cells in fructose medium, and found that the abilities of proliferation and colony formation of glioma cells in fructose medium were similar with abilities in glucose medium, however, fructose just partly restored proliferation ability of normal glial cells. To explore the mechanism, we compared the expression level of GLUT5 (Glucose transporter type 5) in these cell lines, and the results showed that glioma cell lines had higher GLUT5 expression than normal glial cell lines. And knockdown of GLUT5 could significantly inhabit cell proliferation of glioma cells in fructose medium. Furthermore, we found that GLUT5 was also higher expressed in glioma tissues, and GLUT5 expression correlated significantly with glioma malignancy and poor survival of glioma patients (p < 0.01). In addition, we also demonstrated that knockdown of GLUT5 could significantly inhabit tumor proliferation in vivo, and intake fructose could increase tumor volume prominently. Taken together, our data show that fructose can be used by glioma cells, and restrict the fructose intake or targeting GLUT5 could be efficacious strategies in glioma. (C) 2018 Elsevier Inc. All rights reserved.