Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.
Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.
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DOI：
10.1371/journal.pone.0019945
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wadehra M
中科院分区：
文献类型：
--
作者：
Fu M;Rao R;Sudhakar D;Hogue CP;Rutta Z;Morales S;Gordon LK;Braun J;Goodglick L;Wadehra M
子宫内膜癌是发达国家女性中最常见的妇科恶性肿瘤。一种近期发现的与疾病进展和生存密切相关的生物标志物是上皮膜蛋白 - 2（EMP2），这是一种四跨膜蛋白，已知它与某些整合素异构体相关联并能改变其表面表达。在这项研究中，我们利用异种移植模型系统表明，EMP2的表达对于子宫内膜肿瘤的有效形成是必需的，并且我们已经开始描述EMP2促成这种恶性表型的机制。在子宫内膜癌细胞中，通过伤口愈合实验测定，黏着斑激酶（FAK）/Src通路似乎调节细胞迁移。对子宫内膜癌细胞中EMP2水平的调控可调节FAK和Src的磷酸化，并促进它们在脂筏区域的分布。值得注意的是，EMP2水平低的细胞在体内无法迁移且肿瘤形成能力差。这些发现揭示了EMP2在子宫内膜癌发生中的关键作用，并表明EMP2水平升高与子宫内膜癌预后的关联可能与其对整合素介导的信号传导的影响存在因果关系。
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.
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影响因子：
6.2
作者：
Habeeb, Omar;Goodglick, Lee;Soslow, Robert A.;Rao, Rajiv G.;Gordon, Lynn K.;Schirripa, Osvaldo;Horvath, Steve;Braun, Jonathan;Seligson, David B.;Wadehra, Madhuri
通讯作者：
Wadehra, Madhuri
影响因子：
11.5
作者：
Desouki, MM;Rowan, BG
通讯作者：
Rowan, BG
影响因子：
20.3
作者：
Salzer, U;Prohaska, R
通讯作者：
Prohaska, R
DOI：
10.1111/j.1048-891x.2004.014028.x
发表时间：
2004-01-01
影响因子：
4.8
作者：
Gossett, DR;Alo, P;Montz, FJ
通讯作者：
Montz, FJ
影响因子：
3.5
作者：
Hakomori SI
通讯作者：
Hakomori SI