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连接蛋白26的细胞质定位抑制肠道型和混合型胃癌中β-连环蛋白向细胞核的转变。

Cytoplasmic localization of connexin 26 suppresses transition of β-catenin into the nucleus in intestinal- and mix-type gastric cancer.

作者信息

Nakazawa Nobuhiro, Sohda Makoto, Yokobori Takehiko, Gombodorj Navchaa, Sano Akihiko, Sakai Makoto, Oyama Tetsunari, Kuwano Hiroyuki, Shirabe Ken, Saeki Hiroshi

机构信息

Department of General Surgical Science Gunma University Graduate School of Medicine Maebashi Japan.

Division of Integrated Oncology Research Gunma University Initiative for Advanced Research Maebashi Japan.

出版信息

Ann Gastroenterol Surg. 2022 Feb 20;6(4):505-514. doi: 10.1002/ags3.12552. eCollection 2022 Jul.

DOI:10.1002/ags3.12552
PMID:35847440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9271025/
Abstract

BACKGROUND

Connexin is a basic molecule that forms gap junctions and undergoes localization changes to the cytoplasm in association with carcinogenesis. We aimed to investigate and clarify the significance of cytoplasmic Cx26 expression in gastric cancer.

METHODS

We included 87 patients with intestinal- and mix-type gastric cancer and 111 patients with diffuse type gastric cancer who underwent surgery for gastric cancer between 1999 and 2006. Immunohistochemical staining for Cx26, β-catenin, and Wnt3a was performed and analyses of the relationship to clinicopathological factors were conducted based on the Lauren classification. In an in vitro study, the gastric cancer cell lines MKN7, MKN74, and MKN45 were used to evaluate the proliferative capacity using the water-soluble tetrazolium salt assay through forced expression of Cx26, and the relationship between Cx26 and β-catenin was investigated using proximity ligation assay (PLA) and co-immunoprecipitation. Additionally, functional analysis was performed by Cage analysis.

RESULTS

In this study, high cytoplasmic Cx26 expression was associated with favorable prognosis in intestinal- and mix-type gastric cancer and could be an independent prognostic factor for overall survival. In terms of the mechanism, in in vitro experiments changes in Cx26 localization to the cytoplasm were shown to suppress the change of localization of β-catenin to the nucleus by binding to it in the cytoplasm.

CONCLUSIONS

Cytoplasmic Cx26 was found to be a prognostic factor in intestinal- and mix-type gastric cancer. Regarding the mechanism, in vitro studies revealed that cytoplasmic Cx26 inhibits the translocation of β-catenin to the nucleus.

摘要

背景

连接蛋白是一种形成间隙连接并在致癌过程中发生向细胞质定位变化的基础分子。我们旨在研究并阐明细胞质中Cx26表达在胃癌中的意义。

方法

我们纳入了1999年至2006年间接受胃癌手术的87例肠型和混合型胃癌患者以及111例弥漫型胃癌患者。进行了Cx26、β-连环蛋白和Wnt3a的免疫组织化学染色，并基于劳伦分类法对其与临床病理因素的关系进行了分析。在一项体外研究中，使用胃癌细胞系MKN7、MKN74和MKN45，通过强制表达Cx26，采用水溶性四氮唑盐法评估增殖能力，并使用邻近连接法（PLA）和免疫共沉淀法研究Cx26与β-连环蛋白之间的关系。此外，通过Cage分析进行功能分析。

结果

在本研究中，细胞质中Cx26高表达与肠型和混合型胃癌的良好预后相关，并且可能是总生存的独立预后因素。在机制方面，体外实验表明，Cx26向细胞质定位的变化通过在细胞质中与β-连环蛋白结合来抑制其向细胞核的定位变化。

结论

发现细胞质中Cx26是肠型和混合型胃癌的一个预后因素。关于机制，体外研究表明细胞质中Cx26抑制β-连环蛋白向细胞核的转位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/a9b92bad0d52/AGS3-6-505-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/4db458fea5a8/AGS3-6-505-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/b79f4b179ea5/AGS3-6-505-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/afb07f279ebd/AGS3-6-505-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/aeea11d4df93/AGS3-6-505-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/a9b92bad0d52/AGS3-6-505-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/4db458fea5a8/AGS3-6-505-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/b79f4b179ea5/AGS3-6-505-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/afb07f279ebd/AGS3-6-505-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/aeea11d4df93/AGS3-6-505-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/9271025/a9b92bad0d52/AGS3-6-505-g002.jpg

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