Oh Sunhwa, Kim Hyungjoo, Nam KeeSoo, Shin Incheol
Department of Life Science, Hanyang University, Seoul, 133-791, South Korea.
Department of Life Science, Hanyang University, Seoul, 133-791, South Korea; Natural Science Institute, Hanyang University, Seoul, 133-791, South Korea.
Arch Biochem Biophys. 2017 Dec 15;636:110-122. doi: 10.1016/j.abb.2017.08.009. Epub 2017 Aug 10.
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-3β (Ser9)/β-catenin/survivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated.
癌细胞需要增加有氧糖酵解以支持快速的细胞增殖。为满足其增加的能量需求，癌细胞高水平表达葡萄糖转运蛋白（Glut）。Glut1与基底样乳腺癌相关，被认为是一个潜在的治疗靶点。为了研究Glut1作为乳腺癌细胞治疗靶点的可能性，我们使用短发夹系统在三阴性乳腺癌（TNBC）细胞系中下调Glut1。我们确定了Glut1沉默是否可能增强化疗药物的抗增殖作用。与我们的假设相反，Glut1的缺失通过上调p-Akt/p-GSK-3β（Ser9）/β-连环蛋白/存活素减弱了细胞凋亡并增加了耐药性。这些结果表明，应仔细重新评估Glut1作为治疗靶点的潜力。
