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Cancer Lett ; 354(2): 417-26, 2014 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-25150783

RESUMEN

Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial-mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and ß-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with ß-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/ß-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/ß-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/ß-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression.


Asunto(s)
Quimiocina CXCL12/metabolismo , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal , Receptores CXCR4/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Receptores CXCR4/biosíntesis , Receptores CXCR4/genética
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