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

Journal article


Publication Details

Author(s): Hermanns C, Hampl V, Holzer K, Aigner A, Penkava J, Frank N, Martin DE, Maier KC, Waldburger N, Roessler S, Goppelt-Strübe M, Akrap I, Thavamani A, Singer S, Nordheim A, Gudermann T, Muehlich S
Journal: Oncogene
Publication year: 2017
ISSN: 0950-9232


Abstract

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.Oncogene advance online publication, 23 January 2017; doi:10.1038/onc.2016.496.


FAU Authors / FAU Editors

Goppelt-Strübe, Margarete apl. Prof. Dr.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie


How to cite

APA:
Hermanns, C., Hampl, V., Holzer, K., Aigner, A., Penkava, J., Frank, N.,... Muehlich, S. (2017). The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma. Oncogene. https://dx.doi.org/10.1038/onc.2016.496

MLA:
Hermanns, C, et al. "The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma." Oncogene (2017).

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Last updated on 2018-08-10 at 08:31