Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jeric, I; Maurer, G; Cavallo, AL; Raguz, J; Desideri, E; Tarkowski, B; Parrini, M; Fischer, I; Zatloukal, K; Baccarini, M.
A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis.
Nat Commun. 2016; 7(12):13781-13781
Doi: 10.1038/ncomms13781
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- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- Abstract:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, but its molecular heterogeneity hampers the design of targeted therapies. Currently, the only therapeutic option for advanced HCC is Sorafenib, an inhibitor whose targets include RAF. Unexpectedly, RAF1 expression is reduced in human HCC samples. Modelling RAF1 downregulation by RNAi increases the proliferation of human HCC lines in xenografts and in culture; furthermore, RAF1 ablation promotes chemical hepatocarcinogenesis and the proliferation of cultured (pre)malignant mouse hepatocytes. The phenotypes depend on increased YAP1 expression and STAT3 activation, observed in cultured RAF1-deficient cells, in HCC xenografts, and in autochthonous liver tumours. Thus RAF1, although essential for the development of skin and lung tumours, is a negative regulator of hepatocarcinogenesis. This unexpected finding highlights the contribution of the cellular/tissue environment in determining the function of a protein, and underscores the importance of understanding the molecular context of a disease to inform therapy design.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinogenesis - chemically induced
- Carcinogenesis - genetics
- Carcinogenesis - metabolism
- Carcinoma, Hepatocellular - chemically induced
- Carcinoma, Hepatocellular - genetics
- Carcinoma, Hepatocellular - metabolism
- Cell Line, Tumor -
- Cells, Cultured -
- Diethylnitrosamine -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Liver Neoplasms - chemically induced
- Liver Neoplasms - genetics
- Liver Neoplasms - metabolism
- Mice, Knockout -
- Mice, Transgenic -
- Proto-Oncogene Proteins c-raf - genetics
- Proto-Oncogene Proteins c-raf - metabolism
- RNA Interference -
- Signal Transduction - genetics
- Tumor Suppressor Proteins - genetics
- Tumor Suppressor Proteins - metabolism
- Xenograft Model Antitumor Assays -