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Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.

PloS one (2011-06-04)
Maoyong Fu, Rajiv Rao, Deepthi Sudhakar, Claire P Hogue, Zach Rutta, Shawn Morales, Lynn K Gordon, Jonathan Braun, Lee Goodglick, Madhuri Wadehra
ABSTRACT

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methyl-β-cyclodextrin, produced by Wacker Chemie AG, Burghausen, Germany, ≥95.0% cyclodextrin basis (calculated)
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Methyl-β-cyclodextrin, Produced by Wacker Chemie AG, Burghausen, Germany, Life Science, ≥98.0% cyclodextrin basis
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Methyl-β-cyclodextrin, average Mn 1310
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Ponceau S, BioReagent, suitable for electrophoresis
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Methyl-β-cyclodextrin, powder, BioReagent, suitable for cell culture
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