Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells

• Verfasst von: Brauckhoff, Antje [VerfasserIn]
• Verfasst von: Malz, Mona [VerfasserIn]
• Verfasst von: Tschaharganeh, Darjus-Felix [VerfasserIn]
• Verfasst von: Malek, Nisar Peter [VerfasserIn]
• Verfasst von: Weber, Achim [VerfasserIn]
• Verfasst von: Riener, Marc-Oliver [VerfasserIn]
• Verfasst von: Soll, Christopher [VerfasserIn]
• Verfasst von: Samarin, Jana [VerfasserIn]
• Verfasst von: Bissinger, Michaela [VerfasserIn]
• Verfasst von: Schmidt, Jan [VerfasserIn]
• Verfasst von: Longerich, Thomas [VerfasserIn]
• Verfasst von: Ehemann, Volker [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Breuhahn, Kai [VerfasserIn]
• Titel: Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells
• Verf.angabe: 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
• E-Jahr: 2011
• Jahr: 26 February 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 03.06.2022
• Titel Quelle: Enthalten in: Journal of hepatology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1985
• Jahr Quelle: 2011
• Band/Heft Quelle: 55(2011), 5, Seite 1049-1057
• ISSN Quelle: 1600-0641
• DOI: doi:10.1016/j.jhep.2011.02.019
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Brauckhoff, Antje: Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells. - 2011
• Sach-SW: Far-upstream element binding protein
• Sach-SW: FBP-3
• Sach-SW: HCC
• Sach-SW: Hepatocellular carcinoma
• Sach-SW: Proteasome
• Sach-SW: Survival
• Sach-SW: Transcription factor
• K10plus-PPN: 180592043X

Abstract

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.