Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells
Background & Aims - Differential expression of tumor-relevant proteins based on aberrant proteasomal degradation may contribute to human (hepato)carcinogenesis. Recently, we identified the E3 ubiquitin ligase seven in absentia homolog (SIAH)-1 as frequently dysregulated in human hepatocellular c...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
26 February 2011
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| In: |
Journal of hepatology
Year: 2011, Volume: 55, Issue: 5, Pages: 1049-1057 |
| ISSN: | 1600-0641 |
| DOI: | 10.1016/j.jhep.2011.02.019 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jhep.2011.02.019 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0168827811002042 
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| Author Notes: | Antje Brauckhoff, Mona Malz, Darjus Tschaharganeh, Nisar Malek, Achim Weber, Marc-Oliver Riener, Christopher Soll, Jana Samarin, Michaela Bissinger, Jan Schmidt, Thomas Longerich, Volker Ehemann, Peter Schirmacher, Kai Breuhahn |
MARC
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| 245 | 1 | 0 | |a Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells |c Antje Brauckhoff, Mona Malz, Darjus Tschaharganeh, Nisar Malek, Achim Weber, Marc-Oliver Riener, Christopher Soll, Jana Samarin, Michaela Bissinger, Jan Schmidt, Thomas Longerich, Volker Ehemann, Peter Schirmacher, Kai Breuhahn |
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| 520 | |a Background & Aims - Differential expression of tumor-relevant proteins based on aberrant proteasomal degradation may contribute to human (hepato)carcinogenesis. Recently, we identified the E3 ubiquitin ligase seven in absentia homolog (SIAH)-1 as frequently dysregulated in human hepatocellular carcinoma (HCC). We therefore systematically analyzed the expression, functional relevance, as well as possible downstream effectors of SIAH-1 in human liver carcinogenesis. - Methods - SIAH-1 expression was analyzed at the transcript and protein levels in human hepatocarcinogenesis and in HCC cells. Proliferation, apoptosis, and migration of different HCC cell lines were examined after siRNA-mediated inhibition of SIAH-1. In order to identify downstream effectors that mediate SIAH-1 effects, correlative analyses of protein expression profiles were performed. - Results - In HCC tissues both reduction of cytoplasmic SIAH-1 and especially its nuclear accumulation positively correlated with HCC progression. RNA interference revealed that nuclear expression of SIAH-1 predominantly supported HCC cell proliferation and migration while only moderately affecting anti-apoptosis. In de-differentiated human HCCs, nuclear SIAH-1 accumulation significantly correlated with the expression of the transcription factor far-upstream element (FUSE)-binding protein (FBP)-3. In vitro, SIAH-1 positively and indirectly regulated FBP-3 which itself primarily supported HCC cell proliferation. Indeed, high level expression of FBP-3 in human HCCs significantly correlated with reduced overall survival of patients. - Conclusions - Nuclear accumulation of the E3 ubiquitin ligase SIAH-1 supports different pro-tumorigenic cellular processes associated with tumor growth and tumor cell dissemination in human hepatocarcinogenesis. It promotes HCC cell proliferation by at least partly employing the transcription factor FBP-3. Therefore, interference with SIAH-1 activity represents a promising approach to suppress HCC growth. | ||
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