Epithelial membrane protein 3 regulates TGF-β signaling activation in CD44-high glioblastoma.

// Fu Jun 1,* , Jidong Hong 1,* , Qin Liu 2 , Yong Guo 2 , Yiwei Liao 2 , Jianghai Huang 3 , Sailan Wen 3 and Liangfang Shen 1 1 Department of Oncology, Xiangya Hospital, Central South University, Changsha, P. R China 2 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P. R China 3 Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, P. R China * These authors have contributed equally to this work Correspondence: to Liangfang Shen, email: // Keywords : gliblastoma; EMP3; TGF-β; TGFBR2; tumorigenesis Received : May 05, 2016 Accepted : July 19, 2016 Published : August 05, 2016 Abstract Although epithelial membrane protein 3 (EMP3) has been implicated as a candidate tumor suppressor gene for low grade glioma, its biological function in glioblastoma multiforme (GBM) still remains poorly understood. Herein, we showed that EMP3 was highly expressed in CD44-high primary GBMs. Depletion of EMP3 expression suppressed cell proliferation, impaired in vitro tumorigenic potential and induced apoptosis in CD44-high GBM cell lines. We also identified TGF-β/Smad2/3 signaling pathway as a potential target of EMP3. EMP3 interacts with TGF-β receptor type 2 (TGFBR2) upon TGF-β stimulation in GBM cells. Consequently, the EMP3-TGFBR2 interaction regulates TGF-β/Smad2/3 signaling activation and positively impacts on TGF-β-stimulated gene expression and cell proliferation in vitro and in vivo. Highly correlated protein expression of EMP3 and TGF-β/Smad2/3 signaling pathway components was also observed in GBM specimens, confirming the clinical relevancy of activated EMP3/TGF-β/Smad2/3 signaling in GBM. In conclusion, our findings revealed that EMP3 might be a potential target for CD44-high GBMs and highlight the essential functions of EMP3 in TGF-β/Smad2/3 signaling activation and tumor progression.