| First Author | Ohrnberger S | Year | 2015 |
| Journal | Hepatology | Volume | 61 |
| Issue | 3 | Pages | 979-89 |
| PubMed ID | 25266280 | Mgi Jnum | J:317522 |
| Mgi Id | MGI:6855700 | Doi | 10.1002/hep.27539 |
| Citation | Ohrnberger S, et al. (2015) Dysregulated serum response factor triggers formation of hepatocellular carcinoma. Hepatology 61(3):979-89 |
| abstractText | UNLABELLED: The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen-activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF-VP16iHep mice, which conditionally express constitutively active SRF-VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK- and Rho/actin-stimulated target genes. All SRF-VP16iHep mice develop hyperproliferative liver nodules that progresses to lethal HCC. Some murine (m)HCCs acquire Ctnnb1 mutations equivalent to those in human (h)HCC. The resulting transcript signatures mirror those of a distinct subgroup of hHCCs, with shared activation of oncofetal genes including Igf2, correlating with CpG hypomethylation at the imprinted Igf2/H19 locus. CONCLUSION: SRF-VP16iHep mHCC reveal convergent Ras/MAPK and Rho/actin signaling as a highly oncogenic driver mechanism for hepatocarcinogenesis. This suggests simultaneous inhibition of Ras/MAPK and Rho/actin signaling as a treatment strategy in hHCC therapy. |
