Suppressor of fused (Sufu) represses Gli1 transcription and nuclear accumulation, inhibits glioma cell proliferation, invasion and vasculogenic mimicry, improving glioma chemo-sensitivity and prognosis

融合抑制因子 (Sufu) 抑制 Gli1 转录和核积累,抑制神经胶质瘤细胞增殖、侵袭和血管生成拟态,改善神经胶质瘤化学敏感性和预后

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作者:Xing Liu, Xiaofeng Wang, Wenzhong Du, Lingchao Chen, Guangzhi Wang, Yuqiong Cui, Yang Liu, Zhijin Dou, Hongjun Wang, Ping Zhang, Liang Chang, Liye Yi, Jinquan Cai, Chuanlu Jiang

Abstract

Glioblastoma are highly aggressive brain tumors with poor prognosis. While various dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and therapy targets remains an important task for novel diagnostic and therapeutic approaches. Here we described that the Suppressor of fused (also known as Sufu) is significantly down-regulated in high-grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic expression of Sufu inhibited cell proliferation, invasion and vasculogenic mimicry. In addition, overexpression of Sufu reduced Gli reporter gene transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor suppressor and therapeutic target in glioblastoma.

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