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Título

V600EBRAF promotes invasiveness of thyroid cancer cells by decreasing E-cadherin expression through a Snail-dependent mechanism

AutorOrgaz, Jose L.; Jiménez, Benilde ; Chiloeches, Antonio
Fecha de publicación2013
EditorElsevier
CitaciónCancer Letters 335(1): 232-241 (2013)
ResumenBRAF is a main oncogene in human thyroid cancer. Here, we show that BRAF depletion by siRNA or inhibition of its activity by treatment with BRAF inhibitor PLX4720 decreases migration and invasion in thyroid cancer cells expressing oncogenic V600EBRAF through a MEK/ERK-dependent mechanism, since treatment with the MEK inhibitor U0126 exerts the same effect. Moreover, over-expression of V600EBRAF increases migration and invasion of wild-type BRAF thyroid cells. Using the same strategies, we demonstrate that these effects are mediated by upregulation of the transcriptional repressor Snail with a concomitant decrease of its target E-cadherin, both hallmarks of EMT. These results reveal a novel V600EBRAF-induced mechanism in thyroid tumours progression and provides a rationale for using the PLX4720 inhibitor to target V600EBRAF signalling to effectively control progression of thyroid cancer.
URIhttp://hdl.handle.net/10261/124000
DOI10.1016/j.canlet.2013.02.033
Identificadoresdoi: 10.1016/j.canlet.2013.02.033
issn: 0304-3835
e-issn: 1872-7980
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