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Updated: May 13, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
(V600E)BRAF promotes invasiveness of thyroid cancer cells by decreasing E-cadherin expression through a
Pablo Baquero1, Irene Sánchez-Hernández, Eva Jiménez-Mora
1Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
Abstract:
BRAF 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 (V600E)BRAF through a MEK/ERK-dependent mechanism, since treatment with the MEK inhibitor U0126 exerts the same effect. Moreover, over-expression of (V600E)BRAF 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 (V600E)BRAF-induced mechanism in thyroid tumours progression and provides a rationale for using the PLX4720 inhibitor to target (V600E)BRAF signalling to effectively control progression of thyroid cancer.
Insights
Targeting BRAF oncogenes in thyroid cancer with PLX4720 inhibits cancer cell migration and invasion. This BRAF signaling pathway involves MEK/ERK and Snail, offering a new therapeutic strategy for thyroid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- BRAF is a key oncogene implicated in human thyroid cancer development.
- The V600E BRAF mutation is frequently observed in thyroid tumors, driving cancer progression.
Purpose of the Study:
- To investigate the role of BRAF signaling in thyroid cancer cell migration and invasion.
- To explore the underlying molecular mechanisms, including the MEK/ERK pathway and epithelial-mesenchymal transition (EMT).
Main Methods:
- Utilized siRNA to deplete BRAF and pharmacological inhibitors (PLX4720 for BRAF, U0126 for MEK).
- Assessed cell migration and invasion assays.
- Quantified the expression levels of Snail and E-cadherin.
Main Results:
- BRAF inhibition (PLX4720) or depletion (siRNA) reduced thyroid cancer cell migration and invasion.
- These effects were mediated by the MEK/ERK pathway, as confirmed by U0126 treatment.
- Overexpression of V600E BRAF enhanced cell migration and invasion.
- Upregulation of Snail and downregulation of E-cadherin were observed, indicating EMT induction.
Conclusions:
- A novel mechanism of V600E BRAF-induced thyroid tumor progression via Snail/E-cadherin pathway is identified.
- BRAF inhibition presents a promising therapeutic strategy for controlling thyroid cancer progression.
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