Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells.
Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells.
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DOI：
10.1038/oncsis.2017.26
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发表时间：
2017-05-08
期刊：
影响因子：
6.2
通讯作者：
Bhattacharyya A
中科院分区：
文献类型：
--
作者：
Das L;Kokate SB;Dixit P;Rath S;Rout N;Singh SP;Crowe SE;Bhattacharyya A
β-连环蛋白具有两种不同的细胞功能：细胞间粘附和转录活性。E3泛素连接酶Siah 1引起泛素介导的胞质β-连环蛋白降解，因此损害β-连环蛋白的核转位和致癌功能。然而，Siah 1对细胞膜结合的β-catenin的影响尚未研究。在这项研究中，我们确定了致癌细菌H。pylori可增加胃癌细胞（GCCs）MKN 45、AGS和Kato III中ETS 2转录因子介导的Siah 1蛋白表达。与非癌胃上皮相比，胃腺癌活检样品中Siah 1蛋白水平也明显较高。Siah 1基因敲低显著降低了H.幽门感染的胆囊癌虽然Siah 1不能增加β-catenin在细胞内的降解和核转位，但它能增强β-catenin在感染的GCCs中的膜结合降解。β-catenin的膜结合池的丧失与E-钙粘蛋白的蛋白酶体降解无关。因此，这项工作描绘了Siah 1在增加H.幽门感染的胆囊癌
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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DOI：
10.1042/bcj20160187
发表时间：
2016-06-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Das L;Kokate SB;Rath S;Rout N;Singh SP;Crowe SE;Mukhopadhyay AK;Bhattacharyya A
通讯作者：
Bhattacharyya A
影响因子：
8
作者：
Iwai, A;Marusawa, H;Chiba, T
通讯作者：
Chiba, T
影响因子：
10.5
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
5.3
作者：
Frew, IJ;Dickins, RA;Bowtell, DDL
通讯作者：
Bowtell, DDL
影响因子：
3.7
作者：
Kam Y;Quaranta V
通讯作者：
Quaranta V