2024-03-29T05:35:20Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/815922016-02-17T19:32:57Zcom_10261_22com_10261_1col_10261_275
SNAI1 is required for tumor growth and lymph node metastasis of human breast carcinoma MDA-MB-231 cells
Olmeda, David
Moreno-Bueno, Gema
Flores, Juana María
Fabra, Àngels
Portillo, Francisco
Cano, Amparo
The transcription factor, SNAI1 (Snail), has recently been proposed as an important mediator of tumor invasion because of its role in E-cadherin down-regulation and induction of epithelial-mesenchymal transition. In human breast cancer, the expression of SNAI1 and/or the homologous SNAI2 (Slug) has been associated with E-cadherin repression, local or distant metastasis, tumor recurrence, or poor prognosis in different tumor series. However, the specific contribution of either factor to breast tumor progression is still unclear. We have analyzed the role of SNAI1 in human breast cancer by loss of function studies and provide evidence of a major role for SNAI1 in both primary tumor growth and metastasis of human breast carcinoma MDA-MB-231 cells. Specific silencing of SNAI1 by short hairpin RNA induces a decrease in mesenchymal and proinvasive markers (MMP9, ID1, SPARC) in MDA-MB-231 cells, concomitant with reduced in vitro invasive behavior. More importantly, stable SNAI1 silencing in MDA-MB-231 cells leads to a dramatic reduction of in vivo tumor incidence and growth rate. Tumors induced by MDAMB-231-SNAI1-silenced cells show extensive necrotic regions and a significant decrease in invasive and angiogenic markers. Moreover, SNAI1 silencing increases the sensitivity of MDA-MB-231 cells to chemotherapeutics relevant in breast cancer treatments, gemcitabine and docetaxel. Remarkably, analysis of cell lines derived from lymph node metastasis indicates that SNAI1 expression is required for metastatic dissemination. ©2007 American Association for Cancer Research.
Grant support: Spanish Ministry of Education and Science grants SAF2004-00361; NAN2004-09230-C04-02 and EU MRTN-CT-2004-005428 (A. Cano), and Fondo de Investigaciones Sanitarias FIS, PI060194 (A. Fabra). D. Olmeda was funded by a postdoctoral contract from Ministerio de Educación y Ciencia; G. Moreno-Bueno is a junior research contract of the Ramon y Cajal program 2004.
Peer Reviewed
2013-09-06T10:44:43Z
2013-09-06T10:44:43Z
2007
2013-09-06T10:44:43Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1158/0008-5472.CAN-07-2318
issn: 0008-5472
e-issn: 1538-7445
Cancer Research 67(24): 11721-11731 (2007)
http://hdl.handle.net/10261/81592
10.1158/0008-5472.CAN-07-2318
en
none
American Association for Cancer Research