Kindlin-2 interacts with β-catenin and YB-1 to enhance EGFR transcription during glioma progression
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Yunwei Ou1,2,3,4,7, Zitong Zhao2, Weimin Zhang2, Qingnan Wu2, Chuanyue Wu5,6, Xuefeng Liu2, Ming Fu2, Nan Ji1, Dan Wang1, Jiaji Qiu1, Liwei Zhang1, Chunjiang Yu4, Yongmei Song2, Qimin Zhan2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
2State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
3Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
4Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China
5Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA
6Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, South University of Science and Technology of China, Shenzhen, 518055, China
7China National Clinical Research Center for Neurological Diseases, Beijing 100050, China
Chunjiang Yu, email: [email protected]
Yongmei Song, email: [email protected]
Qimin Zhan, email: [email protected]
Keywords: EGFR, glioma, Kindlin-2, transcription
Received: April 20, 2016 Accepted: August 11, 2016 Published: October 04, 2016
Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription. The β-catenin/YB-1/EGFR pathway was required for Kindlin-2-mediated functions. Our data provide a better understanding of the mechanisms underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and therapeutic target in glioma.
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