title: Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Maoyong
authors.initials: M
authors.lastname: Fu
authors.forename: Rajiv
authors.initials: R
authors.lastname: Rao
authors.forename: Deepthi
authors.initials: D
authors.lastname: Sudhakar
authors.forename: Claire P
authors.initials: CP
authors.lastname: Hogue
authors.forename: Zach
authors.initials: Z
authors.lastname: Rutta
authors.forename: Shawn
authors.initials: S
authors.lastname: Morales
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Gordon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.forename: Madhuri
authors.initials: M
authors.lastname: Wadehra
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology*; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D047368:Tumor Burden; D014945:Wound Healing; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C486403:EMP2 protein, human; D008562:Membrane Glycoproteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases