Nichtautonome Effekte des Onkogens YAP in der Hepatokarzinogenese

BackgroundThe transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development.ObjectivesTo investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells.Material and MethodsTranscriptome analysis and proteomi...

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Main Authors: Marquard, Simone (Author) , Thomann, Stefan (Author) , Weiler, Sofia Maria Elisabeth (Author) , Sticht, Carsten (Author) , Gretz, Norbert (Author) , Schirmacher, Peter (Author) , Breuhahn, Kai (Author)
Format: Article (Journal)
Language:German
Published: 2017
In: Der Pathologe
Year: 2017, Volume: 38, Pages: 175-179
ISSN:1432-1963
DOI:10.1007/s00292-017-0361-2
Online Access:Verlag, Volltext: http://dx.doi.org/10.1007/s00292-017-0361-2
Verlag, Volltext: http://link.springer.com/article/10.1007/s00292-017-0361-2
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Author Notes:S. Marquard, S. Thomann, S. M. E. Weiler, C. Sticht, N. Gretz, P. Schirmacher, K. Breuhahn
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Summary:BackgroundThe transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development.ObjectivesTo investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells.Material and MethodsTranscriptome analysis and proteomics of murine wildtype and YAP-transgenic hepatocytes were performed to identify paracrine-acting proteins. Molecular and biochemical techniques were used to examine the mechanisms of YAP-dependent gene regulation. Gene expression data from HCC (hepatocellular carcinoma) patients was evaluated.ResultsSeveral YAP-dependent, secreted factors (e. g. CXCL10, GDF15, PDGFB) were identified. YAP regulates these factors through transcription factors of the TEAD (TEA domain) protein family. Moreover, the dysregulation of the YAP-target genes is often associated with poor HCC patient prognosis.ConclusionsYAP induces the expression of paracrine-acting factors that may affect the tumor microenvironment and therefore support carcinogenesis. This multicellular network could allow the development of novel and specific perturbation approaches.
Item Description:Online publiziert: 10. Oktober 2017
Mit englischer Zusammenfassung unter dem Titel: Nonautonomous effects of oncogenic YAP in hepatocarcinogenesis
Gesehen am 28.06.2018
Physical Description:Online Resource
ISSN:1432-1963
DOI:10.1007/s00292-017-0361-2