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Cell Death Differ ; 27(4): 1225-1242, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31601998

RESUMEN

The RNA-binding protein LIN28B regulates developmental timing and determines stem cell identity by suppressing the let-7 family of microRNAs. Postembryonic reactivation of LIN28B impairs cell commitment to differentiation, prompting their transformation. In this study, we assessed the extent to which ectopic lin28b expression modulates the physiological behavior of neural crest cells (NCC) and governs their transformation in the trunk region of developing embryos. We provide evidence that the overexpression of lin28b inhibits sympathoadrenal cell differentiation and accelerates NCC migration in two vertebrate models, Xenopus leavis and Danio rerio. Our results highlight the relevance of ITGA5 and ITGA6 in the LIN28B-dependent regulation of the invasive motility of tumor cells. The results also establish that LIN28B overexpression supports neuroblastoma onset and the metastatic potential of malignant cells through let-7a-dependent and let-7a-independent mechanisms.


Asunto(s)
Movimiento Celular , Cresta Neural/citología , Proteínas de Unión al ARN/metabolismo , Células Madre/metabolismo , Sistema Simpatoadrenal/citología , Torso/fisiología , Proteínas de Xenopus/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Diferenciación Celular , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Adhesiones Focales/metabolismo , Humanos , Integrinas/metabolismo , Neuronas/citología , Neuronas/metabolismo , Fenotipo , Transducción de Señal , Xenopus laevis , Pez Cebra
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