HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation

// Rui Yang 1 , Yanan Wu 1 , Mei Wang 1 , Zhongfeng Sun 1 , Jiahua Zou 1 , Yundong Zhang 2 , Hongjuan Cui 1 1 State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China 2 Department of Neurosurgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China Correspondence to: Hongjuan Cui, e-mail: hongjuan.cui@gmail.com , hcui@swu.edu.cn Yundong Zhang, e-mail: zhangxh68@sina.com Keywords: HDAC9, TAZ, cell cycle, EGFR, Glioblastoma Received: December 8, 2014      Accepted: January 26, 2015      Published: February 10, 2015 ABSTRACT Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo . HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo . We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.