Oncotarget

Research Papers:

Epithelial membrane protein 3 regulates TGFβ signaling activation in CD44high glioblastoma

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Oncotarget. 2017; 8:14343-14358. https://doi.org/10.18632/oncotarget.11102

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Fu Jun1,*, Jidong Hong1,*, Qin Liu2, Yong Guo2, Yiwei Liao2, Jianghai Huang3, Sailan Wen3 and Liangfang Shen1

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.