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

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-?/Smad2/3 signaling pathway as a potential target of EMP3. EMP3 interacts with TGF-? receptor type 2 (TGFBR2) upon TGF-? stimulation in GBM cells. Consequently, the EMP3-TGFBR2 interaction regulates TGF-?/Smad2/3 signaling activation and positively impacts on TGF-?-stimulated gene expression and cell proliferation in vitro and in vivo. Highly correlated protein expression of EMP3 and TGF-?/Smad2/3 signaling pathway components was also observed in GBM specimens, confirming the clinical relevancy of activated EMP3/TGF-?/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-?/Smad2/3 signaling activation and tumor progression.

SUBMITTER: Jun F 

PROVIDER: S-EPMC5362410 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature