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

// Xing Liu 1, 3, * , Xiaofeng Wang 1, 3, * , Wenzhong Du 1, 3, * , Lingchao Chen 2 , Guangzhi Wang 1, 3 , Yuqiong Cui 1, 3 , Yang Liu 1, 3 , Zhijin Dou 1, 3 , Hongjun Wang 1, 3 , Ping Zhang 1, 3 , Liang Chang 1, 3 , Liye Yi 1, 3 , Jinquan Cai 1, 3 , Chuanlu Jiang 1, 3 1 Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China 3 Chinese Glioma Cooperation Group (CGCG) * These authors contributed equally to this work Correspondence to: Chuanlu Jiang, e-mail: jcl6688@163.com Lingchao Chen, e-mail: chenlingchao12@sina.com Keywords: glioma, Sufu, Gli1, temozolomide, hedgehog Received: April 27, 2014      Accepted: October 10, 2014      Published: October 29, 2014 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.