RNAi-mediated blocking of ezrin reduces migration of ectopic endometrial cells in endometriosis

被引:36
作者
Jiang, Qiao-Ying [1 ]
Xia, Jian-Mei [1 ]
Ding, Hai-Gang [1 ]
Fei, Xiang-Wei [1 ]
Lin, Jun [1 ]
Wu, Rui-Jin [1 ]
机构
[1] Zhejiang Univ, Sch Med, Womens Hosp, Dept Obstet & Gynecol, Hangzhou 310006, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
endometriosis; endometrium; cell culture; RNAi; RHO-GTPASES; EXTRACELLULAR-MATRIX; ESTROGEN-RECEPTOR; ERM PROTEINS; EXPRESSION; CYTOSKELETON; METASTASIS; ACTIVATION; CANCER; CARCINOMA;
D O I
10.1093/molehr/gas019
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ezrin is a member of the ezrinradixinmoesin (ERM) family of membranecytoskeletal linkage proteins. It is important for maintenance of cell shape, adhesion, migration and division. The overexpression of ezrin in some tumours is associated with increased cell migration that is mediated by the Rho/ROCK family of small GTPases. To investigate the role of ezrin in the migration of ectopic endometrial cells in endometriosis, we conducted real-time quantitative RTPCR analysis of the eutopic and ectopic endometrium from women with endometriosis compared with those without the disease. RNAi, wound healing assays and western blot analysis of endometriotic cells were also included in this research. We found significantly higher levels of mRNA expression of ezrin (0.42 versus 0.27, P 0.05), RhoA (0.99 versus 0.74, P 0.05), RhoC (0.79 versus 0.43, P 0.005) and ROCK1 (0.68 versus 0.38, P 0.005) in the ectopic endometrial cells compared with the eutopic endometrial cells in endometriosis. Blocking ezrin with small-interfering RNA reduced the migration of ectopic endometrial cells with decreased expression of RhoA (42.68), RhoC (58.42) and ROCK1 (59.88). Our results indicate that the over-expression of ezrin in endometriosis may play a significant role in the migration of endometrial cells of endometriosis, and the RhoC/Rock pathway may provide a promising treatment target.
引用
收藏
页码:435 / 441
页数:7
相关论文
共 40 条
[1]   Deeply infiltrating endometriosis affecting the rectum and lymph nodes [J].
Abrao, Mauricio S. ;
Podgaec, Sergio ;
Dias, Joao Antonio, Jr. ;
Averbach, Marcelo ;
Garry, Ray ;
Silva, Luis Fernando Ferraz ;
Carvalho, Filomena M. .
FERTILITY AND STERILITY, 2006, 86 (03) :543-547
[2]   Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes [J].
Barrero-Villar, Marta ;
Roman Cabrero, Jose ;
Gordon-Alonso, Monica ;
Barroso-Gonzalez, Jonathan ;
Alvarez-Losada, Susana ;
Angeles Munoz-Fernandez, M. ;
Sanchez-Madrid, Francisco ;
Valenzuela-Fernandez, Agustin .
JOURNAL OF CELL SCIENCE, 2009, 122 (01) :103-113
[3]   The Janus-faced role of ezrin in "linking" cells to either normal or metastatic phenotype [J].
Brambilla, Daria ;
Fais, Stefano .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (10) :2239-2245
[4]   Genomic analysis of metastasis reveals an essential role for RhoC [J].
Clark, EA ;
Golub, TR ;
Lander, ES ;
Hynes, RO .
NATURE, 2000, 406 (6795) :532-535
[5]   Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis [J].
Croft, DR ;
Sahai, E ;
Mavria, G ;
Li, SX ;
Tsai, J ;
Lee, WMF ;
Marshall, CJ ;
Olson, MF .
CANCER RESEARCH, 2004, 64 (24) :8994-9001
[6]   Rho GTPases in cell biology [J].
Etienne-Manneville, S ;
Hall, A .
NATURE, 2002, 420 (6916) :629-635
[7]   Pleiotropic function of ezrin in human metastatic melanomas [J].
Federici, Cristina ;
Brambilla, Daria ;
Lozupone, Francesco ;
Matarrese, Paola ;
de Milito, Angelo ;
Lugini, Luana ;
Iessi, Elisabetta ;
Cecchetti, Serena ;
Marino, Marialucia ;
Perdicchio, Maurizio ;
Logozzi, Mariantonia ;
Spada, Massimo ;
Malorni, Walter ;
Fais, Stefano .
INTERNATIONAL JOURNAL OF CANCER, 2009, 124 (12) :2804-2812
[8]   Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cells [J].
Flamini, M. I. ;
Sanchez, A. M. ;
Goglia, L. ;
Tosi, V. ;
Genazzani, A. R. ;
Simoncini, T. .
MOLECULAR HUMAN REPRODUCTION, 2009, 15 (10) :675-685
[9]   Polarization and Migration of Hematopoietic Stem and Progenitor Cells Rely on the RhoA/ROCK I Pathway and an Active Reorganization of the Microtubule Network [J].
Fonseca, Ana-Violeta ;
Freund, Daniel ;
Bornhaeuser, Martin ;
Corbeil, Denis .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (41) :31661-31671
[10]   Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction [J].
Friel, Anne M. ;
Sexton, Donal J. ;
O'Reilly, Michael W. ;
Smith, Terry J. ;
Morrison, John J. .
REPRODUCTION, 2006, 132 (01) :169-176