title: Epithelial membrane protein 3 regulates TGF-β 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-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.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Fu
authors.initials: F
authors.lastname: Jun
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Jianghai
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Sailan
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, P. R China.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D011379:Prognosis; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C485157:EMP3 protein, human; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta
keywords: EMP3; TGF-β; TGFBR2; gliblastoma; tumorigenesis