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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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
23 January 2017
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| In: |
Oncogene
Year: 2017, Volume: 36, Issue: 24, Pages: 3464-3476 |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/onc.2016.496 |
| Online Access: | Verlag, kostenfrei registrierungspflichtig, Volltext: http://dx.doi.org/10.1038/onc.2016.496 Verlag, kostenfrei registrierungspflichtig, Volltext: https://www.nature.com/articles/onc2016496 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 18.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/onc.2016.496 |