Huang Wenqiu, Zhang Chenguang, Cui Mengtian, Niu Jing, Ding Wei
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China.
Beijing Key Laboratory for Researches in Cancer Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, P.R. China.
Anticancer Res. 2017 Aug;37(8):4285-4294. doi: 10.21873/anticanres.11821.
BACKGROUND/AIM: Bevacizumab (BV) has been used for the treatment of recurrent glioblastoma. However, it also induces epithelial-mesenchymal transition (EMT) in glioblastoma cells, which compromises its efficacy. BATF2 (basic leucine zipper ATF-like transcription factor 2), a multi-target transcriptional repressor, has been found to suppress cancer development partly through inhibition of Wnt/β-catenin singling. The roles of BATF2 and Wnt/β-catenin signaling in BV-induced EMT in glioblastoma cells were investigated in this study.
BV was used to treat U87MG cells, and TOP/FOP FLASH luciferase reporters were employed to determine the activity of Wnt/β-catenin signaling. EMT markers were detected with quantitative reverse transcription-PCR and western blotting. Immunofluorescence (IF) was used to determine the compartmentation of β-catenin. Wound-healing, TransWell and ECIS assays were used to analyze cell adhesion, invasion and migration.
BV induced EMT phenotype in U87MG cells, and BATF2 overexpression significantly inhibited BV-induced EMT with suppression of Wnt/β-catenin signaling.
Our findings expanded the understanding of the role of BATF2 in tumors, and also suggested a potential of using BATF2 as a therapeutic target to hinder bevacizumab induced EMT in glioblastoma.
背景/目的：贝伐单抗（BV）已用于复发性胶质母细胞瘤的治疗。然而，它也会诱导胶质母细胞瘤细胞发生上皮-间质转化（EMT），从而削弱其疗效。BATF2（碱性亮氨酸拉链ATF样转录因子2）是一种多靶点转录抑制因子，已发现其部分通过抑制Wnt/β-连环蛋白信号传导来抑制癌症发展。本研究探讨了BATF2和Wnt/β-连环蛋白信号传导在BV诱导的胶质母细胞瘤细胞EMT中的作用。
用BV处理U87MG细胞，采用TOP/FOP FLASH荧光素酶报告基因检测Wnt/β-连环蛋白信号传导的活性。用定量逆转录PCR和蛋白质印迹法检测EMT标志物。采用免疫荧光（IF）法检测β-连环蛋白的定位。采用伤口愈合实验、TransWell实验和ECIS实验分析细胞黏附、侵袭和迁移能力。
BV诱导U87MG细胞出现EMT表型，BATF2过表达通过抑制Wnt/β-连环蛋白信号传导显著抑制BV诱导的EMT。
我们的研究结果扩展了对BATF2在肿瘤中作用的认识，也提示了将BATF2作为治疗靶点来阻碍贝伐单抗诱导的胶质母细胞瘤EMT的潜力。
