Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression

Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAF(V600E). Through the use of real-time in vivo imaging, we observe disruption...

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Autores principales: Anelli, Viviana, Villefranc, Jacques A, Chhangawala, Sagar, Martinez-McFaline, Raul, Riva, Eleonora, Nguyen, Anvy, Verma, Akanksha, Bareja, Rohan, Chen, Zhengming, Scognamiglio, Theresa, Elemento, Olivier, Houvras, Yariv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Cancer Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389860/
https://www.ncbi.nlm.nih.gov/pubmed/28350298
http://dx.doi.org/10.7554/eLife.20728
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author Anelli, Viviana
Villefranc, Jacques A
Chhangawala, Sagar
Martinez-McFaline, Raul
Riva, Eleonora
Nguyen, Anvy
Verma, Akanksha
Bareja, Rohan
Chen, Zhengming
Scognamiglio, Theresa
Elemento, Olivier
Houvras, Yariv
author_facet Anelli, Viviana
Villefranc, Jacques A
Chhangawala, Sagar
Martinez-McFaline, Raul
Riva, Eleonora
Nguyen, Anvy
Verma, Akanksha
Bareja, Rohan
Chen, Zhengming
Scognamiglio, Theresa
Elemento, Olivier
Houvras, Yariv
author_sort Anelli, Viviana
collection PubMed
description Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAF(V600E). Through the use of real-time in vivo imaging, we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAF(V600E). Adult zebrafish expressing BRAF(V600E) in thyrocytes developed invasive carcinoma. We identified a gene expression signature from zebrafish thyroid cancer that is predictive of disease-free survival in patients with papillary thyroid cancer. Gene expression studies nominated TWIST2 as a key effector downstream of BRAF. Using CRISPR/Cas9 to genetically inactivate a TWIST2 orthologue, we suppressed the effects of BRAF(V600E) and restored thyroid morphology and hormone synthesis. These data suggest that expression of TWIST2 plays a role in an early step of BRAF(V600E)-mediated transformation. DOI: http://dx.doi.org/10.7554/eLife.20728.001
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spelling pubmed-53898602017-04-14 Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression Anelli, Viviana Villefranc, Jacques A Chhangawala, Sagar Martinez-McFaline, Raul Riva, Eleonora Nguyen, Anvy Verma, Akanksha Bareja, Rohan Chen, Zhengming Scognamiglio, Theresa Elemento, Olivier Houvras, Yariv eLife Cancer Biology Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAF(V600E). Through the use of real-time in vivo imaging, we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAF(V600E). Adult zebrafish expressing BRAF(V600E) in thyrocytes developed invasive carcinoma. We identified a gene expression signature from zebrafish thyroid cancer that is predictive of disease-free survival in patients with papillary thyroid cancer. Gene expression studies nominated TWIST2 as a key effector downstream of BRAF. Using CRISPR/Cas9 to genetically inactivate a TWIST2 orthologue, we suppressed the effects of BRAF(V600E) and restored thyroid morphology and hormone synthesis. These data suggest that expression of TWIST2 plays a role in an early step of BRAF(V600E)-mediated transformation. DOI: http://dx.doi.org/10.7554/eLife.20728.001 eLife Sciences Publications, Ltd 2017-03-28 /pmc/articles/PMC5389860/ /pubmed/28350298 http://dx.doi.org/10.7554/eLife.20728 Text en © 2017, Anelli et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Anelli, Viviana
Villefranc, Jacques A
Chhangawala, Sagar
Martinez-McFaline, Raul
Riva, Eleonora
Nguyen, Anvy
Verma, Akanksha
Bareja, Rohan
Chen, Zhengming
Scognamiglio, Theresa
Elemento, Olivier
Houvras, Yariv
Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title_full Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title_fullStr Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title_full_unstemmed Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title_short Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression
title_sort oncogenic braf disrupts thyroid morphogenesis and function via twist expression
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389860/
https://www.ncbi.nlm.nih.gov/pubmed/28350298
http://dx.doi.org/10.7554/eLife.20728
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