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@ARTICLE{Szulzewsky:157169,
author = {F. Szulzewsky and S. Arora and P. Hoellerbauer and C. King
and E. Nathan and M. Chan and P. J. Cimino and T. Ozawa and
D. Kawauchi$^*$ and K. W. Pajtler$^*$ and R. J. Gilbertson
and P. J. Paddison and V. Vasioukhin and T. S. Gujral and E.
C. Holland},
title = {{C}omparison of tumor-associated {YAP}1 fusions identifies
a recurrent set of functions critical for oncogenesis.},
journal = {Genes $\&$ development},
volume = {34},
number = {15-16},
issn = {1549-5477},
address = {Cold Spring Harbor, NY},
publisher = {Laboratory Press},
reportid = {DKFZ-2020-01449},
pages = {1051-1064},
year = {2020},
note = {Volume 34, Issue 15-16, 1 August 2020, Pages 1051-1064},
abstract = {YAP1 is a transcriptional coactivator and the principal
effector of the Hippo signaling pathway, which is causally
implicated in human cancer. Several YAP1 gene fusions have
been identified in various human cancers and identifying the
essential components of this family of gene fusions has
significant therapeutic value. Here, we show that the YAP1
gene fusions YAP1-MAMLD1, YAP1-FAM118B, YAP1-TFE3, and
YAP1-SS18 are oncogenic in mice. Using reporter assays,
RNA-seq, ChIP-seq, and loss-of-function mutations, we can
show that all of these YAP1 fusion proteins exert
TEAD-dependent YAP activity, while some also exert activity
of the C'-terminal fusion partner. The YAP activity of the
different YAP1 fusions is resistant to negative Hippo
pathway regulation due to constitutive nuclear localization
and resistance to degradation of the YAP1 fusion proteins.
Genetic disruption of the TEAD-binding domain of these
oncogenic YAP1 fusions is sufficient to inhibit tumor
formation in vivo, while pharmacological inhibition of the
YAP1-TEAD interaction inhibits the growth of YAP1
fusion-expressing cell lines in vitro. These results
highlight TEAD-dependent YAP activity found in these gene
fusions as critical for oncogenesis and implicate these YAP
functions as potential therapeutic targets in YAP1
fusion-positive tumors.},
cin = {B062},
ddc = {570},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32675324},
doi = {10.1101/gad.338681.120},
url = {https://inrepo02.dkfz.de/record/157169},
}