ORCID Profile
0000-0002-8718-8848
Current Organisations
University of California, San Diego
,
German Cancer Research Center (DKFZ)
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Publisher: Springer Science and Business Media LLC
Date: 02-09-2019
DOI: 10.1038/S41467-019-11884-5
Abstract: YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors.
Publisher: Public Library of Science (PLoS)
Date: 07-02-2013
Publisher: Springer Science and Business Media LLC
Date: 10-05-2019
Publisher: Springer Science and Business Media LLC
Date: 03-11-2016
Publisher: Springer Science and Business Media LLC
Date: 21-07-0001
Publisher: Springer Science and Business Media LLC
Date: 14-03-2018
DOI: 10.1038/NATURE26000
Location: United States of America
Location: United States of America
No related grants have been discovered for Lukas Chavez.