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

Yu 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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 tetra span 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.

Original languageEnglish
Pages (from-to)13974-13985
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number20
DOIs
Publication statusPublished - 2014 May 16
Externally publishedYes

Fingerprint

Glioblastoma
Membrane Proteins
Tumors
Proteins
src-Family Kinases
Therapeutics
Brain
Focal Adhesion Protein-Tyrosine Kinases
Radiotherapy
Cell- and Tissue-Based Therapy
Tumor Burden
Integrins
Brain Neoplasms
Surgery
Cell Movement
Neoplasms
Cells
Antibodies
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma. / Qin, Yu; Fu, Maoyong; Takahashi, Masamichi; Iwanami, Akio; Kuga, Daisuke; Rao, Rajiv G.; Sudhakar, Deepthi; Huang, Tiffany; Kiyohara, Meagan; Torres, Kathleen; Dillard, Christen; Inagaki, Akihito; Kasahara, Noriyuki; Goodglick, Lee; Braun, Jonathan; Mischel, Paul S.; Gordon, Lynn K.; Wadehra, Madhuri.

In: Journal of Biological Chemistry, Vol. 289, No. 20, 16.05.2014, p. 13974-13985.

Research output: Contribution to journalArticle

Qin, Y, Fu, M, Takahashi, M, Iwanami, A, Kuga, D, Rao, RG, Sudhakar, D, Huang, T, Kiyohara, M, Torres, K, Dillard, C, Inagaki, A, Kasahara, N, Goodglick, L, Braun, J, Mischel, PS, Gordon, LK & Wadehra, M 2014, 'Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma', Journal of Biological Chemistry, vol. 289, no. 20, pp. 13974-13985. https://doi.org/10.1074/jbc.M113.543728
Qin, Yu ; Fu, Maoyong ; Takahashi, Masamichi ; Iwanami, Akio ; Kuga, Daisuke ; Rao, Rajiv G. ; Sudhakar, Deepthi ; Huang, Tiffany ; Kiyohara, Meagan ; Torres, Kathleen ; Dillard, Christen ; Inagaki, Akihito ; Kasahara, Noriyuki ; Goodglick, Lee ; Braun, Jonathan ; Mischel, Paul S. ; Gordon, Lynn K. ; Wadehra, Madhuri. / Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 20. pp. 13974-13985.
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