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

Brauckhoff, Antje; Malz, Mona; Tschaharganeh, Darjus F.; Malek, Nisar P.; Weber, Achim; Riener, Marc‐Oliver; Soll, Christopher; Samarin, Jana; Bissinger, Michaela; Schmidt, Jan; Longerich, Thomas; Ehemann, Volker; Schirmacher, Peter; Breuhahn, Kai

doi:10.1016/j.jhep.2011.02.019

Cited by 38 publications

(54 citation statements)

References 29 publications

(53 reference statements)

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“…Another study in breast cancer also showed that increased Siah expression was related to the aggressiveness of breast cancers [24]. Similarly, Siah1 nuclear expression was shown to be positively correlated with hepatocellular cancer progression [25]. These studies support our current results that Siah1 expression itself may influence the progression of NPC.…”

Section: Discussionsupporting

confidence: 85%

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Expression of seven-in-absentia homologue 1 and hypoxia-inducible factor 1 alpha: Novel prognostic factors of nasopharyngeal carcinoma

et al. 2013

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(T. Yoshizaki). Keywords:seven-in-absentia homologue 1 (Siah1) hypoxia-inducible factor 1 alpha (HIF1α) latent membrane protein 1 (LMP1) Epstein-Barr virus (EBV) nasopharyngeal carcinoma ABSTRACT Nasopharyngeal carcinoma (NPC) is an EBV-associated cancer. We analysed Siah1 expression as well as LMP1 and HIF1α expression by immuno-histochemical staining in 74 NPC biopsy specimens and found that the expression of Siah1 was significantly correlated with advanced tumour status and stage. Moreover, Siah1-positive and HIF1α-positive cases had significantly worse prognoses. The expression score for LMP1 was remarkably correlated with that of Siah1, whereas there was little correlation between LMP1 expression and the other markers evaluated. This is the first study to evaluate the pattern and clinical significance of Siah1 and HIF1α expression in NPC, and such an evaluation is valuable for identifying those patients at a high risk for a poor prognosis.

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Section: Discussionsupporting

confidence: 85%

“…Moreover, understanding the molecular mechanisms that regulate Siah expression will likely provide new insights into the pivotal function of Siah in cancer biology and should contribute to novel anti-cancer strategies [12,13,25]. The relationship between Siah1 and HIF1α expression and patient prognosis was examined by Kaplan-Meier analysis.…”

Section: Discussionmentioning

confidence: 99%

Expression of seven-in-absentia homologue 1 and hypoxia-inducible factor 1 alpha: Novel prognostic factors of nasopharyngeal carcinoma

et al. 2013

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“…These proteins modulate several cellular functions including angiogenesis, inflammation, cell proliferation, cell migration and apoptosis. 1, 2, 3, 4, 5 Humans have siah1 , siah2 and siah3 genes whereas, mice have siah1a , siah1b and siah2 genes. 6, 7 Animal model-based studies support oncogenic functions of both Siah1 and Siah2 while tumor-promoting roles of Siah2 and apoptosis-inducing role of Siah1 are mostly reported from cell line-based assays.…”

Section: Introductionmentioning

confidence: 99%

Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells

et al. 2017

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β-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic β-catenin and therefore, impairs nuclear translocation and oncogenic function of β-catenin. However, the effect of Siah1 on the cell membrane bound β-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III. Siah1 protein level was also noticeably higher in gastric adenocarcinoma biopsy samples as compared to non-cancerous gastric epithelia. Siah1 knockdown significantly decreased invasiveness and migration of H. pylori-infected GCCs. Although, Siah1 could not increase degradation of the cytosolic β-catenin and its nuclear translocation, it enhanced degradation of the membrane-bound β-catenin in the infected GCCs. This loss of membrane-bound pool of β-catenin was not associated with the proteasomal degradation of E-cadherin. Thus, this work delineated the role of Siah1 in increasing invasiveness of H. pylori-infected GCCs.

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“…After that, Malz and his colleagues found a reduction of cytoplasmic SIAH1 but an accumulation of nuclear SIAH1 in HCC tissues. Nuclear accumulation of SIAH1 supports different pro-tumorigenic processes in human hepatocarcinogenesis in vitro, and promotes HCC cell proliferation by partly employing the transcription factor FBP3 (far-upstream element binding protein 3) [66]. The nuclear accumulation of SIAH2 is also detectable in most HCCs and correlates with tumor progression, and reduction of the SIAH2 expression increases the response of HCC cells to different cytostatic drugs, representing a promising therapeutic strategy for HCC [67].…”

Section: The Ubiquitin Enzymementioning

confidence: 99%

The ubiquitin–proteasome system and its potential application in hepatocellular carcinoma therapy

Chen

Shen

2016

Cancer Letters

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

Cited by 38 publications

References 29 publications

Expression of seven-in-absentia homologue 1 and hypoxia-inducible factor 1 alpha: Novel prognostic factors of nasopharyngeal carcinoma

Expression of seven-in-absentia homologue 1 and hypoxia-inducible factor 1 alpha: Novel prognostic factors of nasopharyngeal carcinoma

Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells

The ubiquitin–proteasome system and its potential application in hepatocellular carcinoma therapy

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