Silencing of Glut1 induces chemoresistance via modulation of Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells

被引：31
作者：
Oh, Sunhwa [1 ]
Kim, Hyungjoo [1 ]
Nam, KeeSoo [1 ]
Shin, Incheol [1 ,2 ]
机构：
[1] Hanyang Univ, Dept Life Sci, Seoul 133791, South Korea
[2] Hanyang Univ, Inst Nat Sci, Seoul 133791, South Korea
来源：
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2017年 / 636卷
关键词：
Glut1; Chemoresistance; Triple-negative breast cancer; GLYCOGEN-SYNTHASE KINASE-3; GROWTH-FACTOR RECEPTOR; GLUCOSE TRANSPORTERS; COLORECTAL-CANCER; EGR-1; EXPRESSION; GENE-EXPRESSION; SUGAR-TRANSPORT; POOR-PROGNOSIS; CARCINOMA; SURVIVIN;
D O I：
10.1016/j.abb.2017.08.009
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Cancer cells require increased aerobic glycolysis to support rapid cell proliferation. For their increased energy demands, cancer cells express glucose transporter (Glut) proteins at a high level. Glut1 is associated with basal-like breast cancer and is considered a potential therapeutic target. To investigate the possibility of Glut1 as a therapeutic target in breast cancer cells, we downregulated Glut1 in triple negative breast cancer (TNBC) cell lines using a short hairpin system. We determined whether Glut1 silencing might enhance anti-proliferative effect of chemotherapeutic agents. Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3 beta (Ser9)/beta-cateninisurvivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated. (C) 2017 Published by Elsevier Inc.
引用
收藏
页码：110 / 122
页数：13
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