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Barbosa, I.A.M.* ; Gopalakrishnan, R.* ; Mercan, S.* ; Mourikis, T.P.* ; Martin, T.* ; Wengert, S. ; Sheng, C.* ; Ji, F.* ; Lopes, R.* ; Knehr, J.* ; Altorfer, M.* ; Lindeman, A.* ; Russ, C.* ; Naumann, U.* ; Golji, J.* ; Sprouffske, K.* ; Barys, L.* ; Tordella, L.* ; Schübeler, D.* ; Schmelzle, T.* ; Galli, G.G.*

Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens.

Nat. Commun. 14:3907 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
YAP is a key transcriptional co-activator of TEADs, it regulates cell growth and is frequently activated in cancer. In Malignant Pleural Mesothelioma (MPM), YAP is activated by loss-of-function mutations in upstream components of the Hippo pathway, while, in Uveal Melanoma (UM), YAP is activated in a Hippo-independent manner. To date, it is unclear if and how the different oncogenic lesions activating YAP impact its oncogenic program, which is particularly relevant for designing selective anti-cancer therapies. Here we show that, despite YAP being essential in both MPM and UM, its interaction with TEAD is unexpectedly dispensable in UM, limiting the applicability of TEAD inhibitors in this cancer type. Systematic functional interrogation of YAP regulatory elements in both cancer types reveals convergent regulation of broad oncogenic drivers in both MPM and UM, but also strikingly selective programs. Our work reveals unanticipated lineage-specific features of the YAP regulatory network that provide important insights to guide the design of tailored therapeutic strategies to inhibit YAP signaling across different cancer types.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hippo Signaling Pathway; Uveal Melanoma; Size-control; Organ Size; Mutations; Activation; Induction; Biology; Growth; Ap-1
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 14, Heft: 1, Seiten: , Artikelnummer: 3907 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Pioneer Campus (HPC)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Pioneer Campus
PSP-Element(e) G-510007-001
Förderungen Swiss National Science Foundation (SNF)
European Research Council
Swiss National Science Foundation
Novartis Research Foundation
DOI 10.1038/s41467-023-39527-w
WOS ID 001028011500031
Scopus ID 85163796624
PubMed ID 37400441
Erfassungsdatum 2023-10-18
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