Jian Wang1,2,3,4, Xingang Li5,6,7, Tao Luo1,2, Kaikai Ding1,2, Jianxiong Ji1,2, Xin Zhang1,2, Xiaobing Yang1,2, Anjing Chen1,2,8, Bin Huang1,2, Di Zhang1,2. 1. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Cheeloo College of Medicine, Shandong University, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China. 2. Key Laboratory of Brain Functional Remodeling, Shandong, 250012, Jinan, China. 3. Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009, Bergen, Norway. 4. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China. 5. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Cheeloo College of Medicine, Shandong University, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China. lixg@sdu.edu.cn. 6. Key Laboratory of Brain Functional Remodeling, Shandong, 250012, Jinan, China. lixg@sdu.edu.cn. 7. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, 107# Wenhua Xi Road, Shandong, 250012, Jinan, China. lixg@sdu.edu.cn. 8. School of Medicine, Shandong University, Shandong, China.
Abstract
PURPOSE: Gliomas are the most common and aggressive malignant brain tumors and are associated with high mortality and incidence in humans. Despite rigorous multi-modal therapy, including surgery, chemotherapy and radiotherapy, patients with malignant glioma survive an average of 12-15 months following primary diagnosis. Therefore, new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we find that suppression of CKAP4 might inhibit glioma growth through regulation of Hippo signaling. METHODS: We examined the expression levels of CKAP4 through analysis of RNA sequencing data from GEPIA and CGGA databases. Then, Lentivirus was used to construct stable cell lines with knockout or overexpression of CKAP4. Next, the function of CKAP4 on glioma was investigated in vitro and in an orthotopic brain tumor model in mice. Lastly, luciferase reporter assay, immunofluorescence and immunoblotting were performed to explore the potential mechanism of how CKAP4 affects gliomas. RESULTS: CKAP4 is highly upregulated in glioma and high CKAP4 expressing tumors were associated with poor patient survival. And CKAP4 promotes malignant progression of gliomas via inhibiting Hippo signaling. CONCLUSION: CKAP4 has potential as a promising biomarker and can predict the prognosis of patients with gliomas. And targeting CKAP4 expression may be an effective therapeutic strategy for the treatment of human gliomas.
PURPOSE: Gliomas are the most common and aggressive malignant brain tumors and are associated with high mortality and incidence in humans. Despite rigorous multi-modal therapy, including surgery, chemotherapy and radiotherapy, patients with malignant glioma survive an average of 12-15 months following primary diagnosis. Therefore, new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we find that suppression of CKAP4 might inhibit glioma growth through regulation of Hippo signaling. METHODS: We examined the expression levels of CKAP4 through analysis of RNA sequencing data from GEPIA and CGGA databases. Then, Lentivirus was used to construct stable cell lines with knockout or overexpression of CKAP4. Next, the function of CKAP4 on glioma was investigated in vitro and in an orthotopic brain tumor model in mice. Lastly, luciferase reporter assay, immunofluorescence and immunoblotting were performed to explore the potential mechanism of how CKAP4 affects gliomas. RESULTS: CKAP4 is highly upregulated in glioma and high CKAP4 expressing tumors were associated with poor patient survival. And CKAP4 promotes malignant progression of gliomas via inhibiting Hippo signaling. CONCLUSION: CKAP4 has potential as a promising biomarker and can predict the prognosis of patients with gliomas. And targeting CKAP4 expression may be an effective therapeutic strategy for the treatment of human gliomas.
Authors: Erwin G Van Meir; Costas G Hadjipanayis; Andrew D Norden; Hui-Kuo Shu; Patrick Y Wen; Jeffrey J Olson Journal: CA Cancer J Clin Date: 2010 May-Jun Impact factor: 508.702