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| Título: | Site-dependent E-cadherin cleavage and nuclear translocation in a metastatic colorectal cancer model |
Autor: | Céspedes, María Virtudes; Larriba, María Jesús CSIC ORCID; Muñoz Terol, Alberto CSIC ORCID; Mangues, Ramón | Fecha de publicación: | 2010 | Editor: | American Society for Investigative Pathology Elsevier |
Citación: | American Journal of Pathology 177(4): 2067-2079 (2010) | Resumen: | Metastases are frequently found during colorectal cancer diagnoses and are the main determinants of clinical outcome. The lack of reliable models of metastases has precluded their mechanistic understanding and our capacity to improve outcome. We studied the effect of E-cadherin and Snail1 expression on metastagenesis in a colorectal cancer model. We microinjected SW480-ADH human colorectal cancer cells, transfected with an empty vector (Mock) or overexpressing Snail1 (Snail1OE) or E-cadherin (E-cadherin OE), in the ceca of nude mice (eight per group) and analyzed tumor growth, dissemination, and Snail1, E-cadherin, β-catenin, and Presenilin1 (PS1) expression in local tumors and/or metastatic foci. Snail1OE cells disseminated only to lymph nodes, whereas Mock or E-cadherinOE cells spread to lymph nodes and peritoneums. Peritoneal tumor foci developed by E-cadherinOE cells presented an increase in E-cadherin proteolysis and nuclear translocation, and enhanced expression of proteolytically active PS1, which was linked to increased tumor growth and shortened mouse survival. Interestingly, local and lymph node tumors in mice bearing E-cadherin OE cells overexpressed E-cadherin, but they did not show Ecadherin proteolysis or nuclear translocation. Remarkably, E-cadherin nuclear translocation and enhanced expression of active PS1 were found in a patient with colorectal signet-ring cell carcinoma. In conclusion, we have established a colorectal cancer metastasis model in which E-cadherin proteolyis and nuclear translocation associates with aggressive foci growth only in the peritoneal microenvironment. Copyright © American Society for Investigative Pathology. | Descripción: | El pdf del artículo es la versión pre-print.-- et al. | Versión del editor: | http://dx.doi.org/10.2353/ajpath.2010.100079 | URI: | http://hdl.handle.net/10261/77879 | DOI: | 10.2353/ajpath.2010.100079 | Identificadores: | doi: 10.2353/ajpath.2010.100079 issn: 0002-9440 e-issn: 1525-2191 |
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| Site-Dependent.pdf | 2,38 MB | Adobe PDF |  Visualizar/Abrir |
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