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The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profi...

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Bibliographische Detailangaben
Hauptverfasser: Hermanns, Constanze (VerfasserIn) , Holzer, Kerstin (VerfasserIn) , Waldburger, Nina (VerfasserIn) , Rössler, Stephanie (VerfasserIn) , Singer, Stephan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 23 January 2017
In: Oncogene
Year: 2017, Jahrgang: 36, Heft: 24, Pages: 3464-3476
ISSN:1476-5594
DOI:10.1038/onc.2016.496
Online-Zugang:Verlag, kostenfrei registrierungspflichtig, Volltext: http://dx.doi.org/10.1038/onc.2016.496
Verlag, kostenfrei registrierungspflichtig, Volltext: https://www.nature.com/articles/onc2016496
Volltext
Verfasserangaben:C. Hermanns, V. Hampl, K. Holzer, A. Aigner, J. Penkava, N. Frank, D.E. Martin, K.C. Maier, N. Waldburger, S. Roessler, M. Goppelt-Struebe, I. Akrap, A. Thavamani, S. Singer, A. Nordheim, T. Gudermann, S. Muehlich
Beschreibung
Zusammenfassung:Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.
Beschreibung:Gesehen am 18.05.2018
Beschreibung:Online Resource
ISSN:1476-5594
DOI:10.1038/onc.2016.496

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