斑马鱼
癌症研究
甲状腺癌
甲状腺癌
生物
甲状腺
V600E型
效应器
突变
基因
细胞生物学
内分泌学
遗传学
作者
Viviana Anelli,Jacques A. Villefranc,Sagar Chhangawala,Raúl Martinez-McFaline,Eleonora Riva,Anvy Nguyen,Akanksha Verma,Rohan Bareja,Zhengming Chen,Theresa Scognamiglio,Olivier Elemento,Yariv Houvras
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2017-03-28
卷期号:6
被引量:46
摘要
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.
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