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三胞融合蛋白表达与结直肠癌不良预后和转移相关。

Association of tricellulin expression with poor colorectal cancer prognosis and metastasis.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):2174-2184. doi: 10.3892/or.2020.7773. Epub 2020 Sep 17.

Abstract

Tricellulin is a tight‑junction transmembrane protein that regulates cell‑cell interactions. Altered tricellulin expression could promote tumor cell invasions and metastasis in human cancers. The present study assessed tricellulin expression in colorectal cancer tissues for any association with clinicopathological features of colorectal cancer patients and then investigated the underlying molecular events using quantitative proteomic analysis and in vitro experiments. Tissue samples from 98 colorectal cancer patients and 15 volunteers were collected for immunohistochemistry. Colorectal cell lines were used to overexpress or knockdown tricellulin expression in various assays. The data revealed that upregulated tricellulin expression was associated with lymph node and distant metastases and poor prognosis, while tricellulin overexpression promoted colorectal cancer cell migration and invasion in vitro. In contrast, tricellulin knockdown had positive effects on the tumor cells. Furthermore, TMT‑LC‑MS/MS and bioinformatics analyses revealed that tricellulin was involved in EMT and reduction of apoptosis through the NF‑κB signaling pathway. These findings highlight for the first time the significance of tricellulin in colorectal cancer development and progression. Further study may validate tricellulin as a novel biomarker and target for colorectal cancer.

摘要

三钙黏蛋白是一种紧密连接跨膜蛋白,可调节细胞间相互作用。三钙黏蛋白表达的改变可促进人类癌症中的肿瘤细胞侵袭和转移。本研究评估了结直肠癌组织中三钙黏蛋白的表达情况,以了解其与结直肠癌患者临床病理特征的关系,然后使用定量蛋白质组学分析和体外实验研究了潜在的分子事件。收集了 98 例结直肠癌患者和 15 名志愿者的组织样本进行免疫组织化学分析。使用结直肠癌细胞系在各种实验中过表达或敲低三钙黏蛋白的表达。结果表明,上调的三钙黏蛋白表达与淋巴结和远处转移以及预后不良有关,而过表达三钙黏蛋白可促进结直肠癌细胞的迁移和侵袭。相比之下,三钙黏蛋白的敲低对肿瘤细胞有积极影响。此外,TMT-LC-MS/MS 和生物信息学分析表明,三钙黏蛋白通过 NF-κB 信号通路参与 EMT 和减少细胞凋亡。这些发现首次强调了三钙黏蛋白在结直肠癌发生和发展中的重要性。进一步的研究可能会验证三钙黏蛋白作为结直肠癌的新型生物标志物和治疗靶点的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7724/7551433/60b58c2a6869/OR-44-05-2174-g00.jpg

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