In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-03-28)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.20728.001
DOI:
10.7554/eLife.20728.002
DOI:
10.7554/eLife.20728.003
DOI:
10.7554/eLife.20728.004
DOI:
10.7554/eLife.20728.005
DOI:
10.7554/eLife.20728.006
DOI:
10.7554/eLife.20728.007
DOI:
10.7554/eLife.20728.008
DOI:
10.7554/eLife.20728.009
DOI:
10.7554/eLife.20728.010
DOI:
10.7554/eLife.20728.011
DOI:
10.7554/eLife.20728.012
DOI:
10.7554/eLife.20728.013
DOI:
10.7554/eLife.20728.014
DOI:
10.7554/eLife.20728.015
DOI:
10.7554/eLife.20728.016
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3