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Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma.

Abstract
Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvβ3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.
AuthorsYu Qin, Maoyong Fu, Masamichi Takahashi, Akio Iwanami, Daisuke Kuga, Rajiv G Rao, Deepthi Sudhakar, Tiffany Huang, Meagan Kiyohara, Kathleen Torres, Christen Dillard, Akihito Inagaki, Noriyuki Kasahara, Lee Goodglick, Jonathan Braun, Paul S Mischel, Lynn K Gordon, Madhuri Wadehra
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 20 Pg. 13974-85 (May 16 2014) ISSN: 1083-351X [Electronic] United States
PMID24644285 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References
  • EMP2 protein, human
  • Membrane Glycoproteins
  • Focal Adhesion Kinase 1
  • src-Family Kinases
Topics
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Activation
  • Female
  • Focal Adhesion Kinase 1 (metabolism)
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma (drug therapy, enzymology, metabolism, pathology)
  • Humans
  • Membrane Glycoproteins (immunology, metabolism)
  • Mice
  • Molecular Targeted Therapy
  • Phenotype
  • src-Family Kinases (metabolism)

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