Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Lanaya, H; Natarajan, A; Komposch, K; Li, L; Amberg, N; Chen, L; Wculek, SK; Hammer, M; Zenz, R; Peck-Radosavljevic, M; Sieghart, W; Trauner, M; Wang, H; Sibilia, M.
EGFR has a tumour-promoting role in liver macrophages during hepatocellular carcinoma formation.
Nat Cell Biol. 2014; 16(10): 1- 7.
Doi: 10.1038/ncb3031
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- Co-authors Med Uni Graz
- Trauner Michael
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- Abstract:
- Hepatocellular carcinoma (HCC) is a frequent cancer with limited treatment options and poor prognosis. Tumorigenesis has been linked with macrophage-mediated chronic inflammation and diverse signalling pathways, including the epidermal growth factor receptor (EGFR) pathway. The precise role of EGFR in HCC is unknown, and EGFR inhibitors have shown disappointing clinical results. Here we discover that EGFR is expressed in liver macrophages in both human HCC and in a mouse HCC model. Mice lacking EGFR in macrophages show impaired hepatocarcinogenesis, whereas mice lacking EGFR in hepatocytes unexpectedly develop more HCC owing to increased hepatocyte damage and compensatory proliferation. Mechanistically, following interleukin-1 stimulation, EGFR is required in liver macrophages to transcriptionally induce interleukin-6, which triggers hepatocyte proliferation and HCC. Importantly, the presence of EGFR-positive liver macrophages in HCC patients is associated with poor survival. This study demonstrates a tumour-promoting mechanism for EGFR in non-tumour cells, which could lead to more effective precision medicine strategies.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Blotting, Western -
- Carcinoma, Hepatocellular - chemically induced Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism
- Cells, Cultured -
- Diethylnitrosamine -
- Hepatocytes - metabolism
- Humans -
- Immunohistochemistry -
- Interleukin-1beta - pharmacology
- Kupffer Cells - drug effects Kupffer Cells - metabolism
- Liver - metabolism Liver - pathology
- Liver Neoplasms - chemically induced Liver Neoplasms - genetics Liver Neoplasms - metabolism
- Macrophages - metabolism
- Male -
- Mice, 129 Strain -
- Mice, Inbred C57BL -
- Mice, Inbred CBA -
- Mice, Knockout -
- Mice, Transgenic -
- Phosphorylation - drug effects
- Receptor, Epidermal Growth Factor - genetics Receptor, Epidermal Growth Factor - metabolism