Wenqiu Huang1, Chenguang Zhang1,2, Mengtian Cui1, Jing Niu1, Wei Ding3,2,4. 1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China. 2. Beijing Key Laboratory for Researches in Cancer Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, P.R. China. 3. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China weiding@ccmu.edu.cn. 4. Beijing Institute of Brain Disorders, Beijing, P.R. China.
Abstract
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. MATERIALS AND METHODS: 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. RESULTS: BV induced EMT phenotype in U87MG cells, and BATF2 overexpression significantly inhibited BV-induced EMT with suppression of Wnt/β-catenin signaling. CONCLUSION: 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. Copyright
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. MATERIALS AND METHODS: 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. RESULTS: BV induced EMT phenotype in U87MG cells, and BATF2 overexpression significantly inhibited BV-induced EMT with suppression of Wnt/β-catenin signaling. CONCLUSION: 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. Copyright
Authors: Wei Xie; Yan Zhang; Shiwei Zhang; Fengxian Wang; Kunchi Zhang; Yanjuan Huang; Zhaoli Zhou; Gang Huang; Jin Wang Journal: Am J Cancer Res Date: 2019-08-01 Impact factor: 6.166