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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Álvarez-Díaz, S. | - |
dc.contributor.author | Valle, Noelia | - |
dc.contributor.author | García, José M. | - |
dc.contributor.author | Peña, Cristina | - |
dc.contributor.author | Freije, José M. P. | - |
dc.contributor.author | Quesada, Víctor | - |
dc.contributor.author | Astudillo, Aurora | - |
dc.contributor.author | Bonilla, Félix | - |
dc.contributor.author | López-Otín, Carlos | - |
dc.contributor.author | Muñoz Terol, Alberto | - |
dc.date.accessioned | 2010-05-31T12:11:14Z | - |
dc.date.available | 2010-05-31T12:11:14Z | - |
dc.date.issued | 2009-08 | - |
dc.identifier.citation | Journal of Clinical Investigation 119(8): 2343-2358 (2009) | en_US |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | http://hdl.handle.net/10261/24884 | - |
dc.description | 16 pages, 11 figures. | en_US |
dc.description.abstract | The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1α,25(OH)2D3 action on human colon cancer cells revealed cystatin D (CST5), which encodes an inhibitor of several cysteine proteases of the cathepsin family, as a candidate target gene. Here we report that 1α,25(OH)2D3 induced vitamin D receptor (VDR) binding to, and activation of, the CST5 promoter and increased CST5 RNA and protein levels in human colon cancer cells. In cells lacking endogenous cystatin D, ectopic cystatin D expression inhibited both proliferation in vitro and xenograft tumor growth in vivo. Furthermore, cystatin D inhibited migration and anchorage-independent growth, antagonized the Wnt/β-catenin signaling pathway, and repressed c-MYC expression. Cystatin D repressed expression of the epithelial-mesenchymal transition inducers SNAI1, SNAI2, ZEB1, and ZEB2 and, conversely, induced E-cadherin and other adhesion proteins. CST5 knockdown using shRNA abrogated the antiproliferative effect of 1α,25(OH)2D3, attenuated E-cadherin expression, and increased c-MYC expression. In human colorectal tumors, expression of cystatin D correlated with expression of VDR and E-cadherin, and loss of cystatin D correlated with poor tumor differentiation. Based on these data, we propose that CST5 has tumor suppressor activity that may contribute to the antitumoral action of 1α,25(OH)2D3 in colon cancer. | en_US |
dc.description.sponsorship | This work was supported by the Ministerio de Ciencia e Innovación (SAF2007-60341, SAF2006-00476, ISCIII-RETIC RD06/0020/0009, and RD06/0020/0020), Comunidad de Madrid (S-GEN-0266/2006), and the European Union (MRTN-CT-2005-019496, NucSys and Micoenvimet, FP7). The Instituto Universitario de Oncología and Hospital Universitario Central de Asturias tumor bank are supported by Obra Social Cajastur and Acción Transversal del Cáncer–RTICC. | en_US |
dc.format.extent | 5990725 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | en_US |
dc.publisher | American Society for Clinical Investigation | en_US |
dc.rights | openAccess | en_US |
dc.title | Cystatin D is a candidate tumor suppressor gene induced by vitamin D in human colon cancer cells | en_US |
dc.type | artículo | en_US |
dc.identifier.doi | 10.1172/JCI37205 | - |
dc.description.peerreviewed | Peer reviewed | en_US |
dc.relation.publisherversion | http://dx.doi.org/10.1172/JCI37205 | en_US |
dc.identifier.pmid | 19662683 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
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Cystatin D.pdf | 5,85 MB | Adobe PDF | Visualizar/Abrir |
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