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肿瘤内皮标志物8通过Wnt/β-连环蛋白信号通路促进肺腺癌的增殖和转移。

Tumor Endothelial Marker 8 Promotes Proliferation and Metastasis the Wnt/β-Catenin Signaling Pathway in Lung Adenocarcinoma.

作者信息

Ding Chen, Liu Jun, Zhang Jiali, Wan Yang, Hu Linhui, Charwudzi Alice, Zhan Heqin, Meng Ye, Zheng Huimin, Wang HuiPing, Wang Youliang, Gao Lihua, Hu Xianwen, Li Jingrong, Xiong Shudao

机构信息

Department of Hematology/Oncology Lab, The Second Hospital of Anhui Medical University, Hefei, China.

Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

出版信息

Front Oncol. 2021 Oct 14;11:712371. doi: 10.3389/fonc.2021.712371. eCollection 2021.

Abstract

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What's more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/β-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/β-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.

摘要

肿瘤内皮标志物8(TEM8),也被称为血管生成素样蛋白1(ANTXR1),在癌症中高表达,并被确定为某些癌症早期诊断和预后的生物标志物。然而,TEM8在肺腺癌(LUAD)中的临床作用和分子机制仍不清楚。本研究旨在探讨其临床价值以及TEM8在LUAD进展中的分子机制。我们的研究发现LUAD细胞系和组织中TEM8升高。此外,我们观察到TEM8表达水平与肿瘤大小、原发肿瘤和美国癌症联合委员会(AJCC)分期相关,TEM8高表达的LUAD患者通常预后较差。然后,我们通过功能丧失和功能获得策略进行了一系列实验,结果表明,敲低TEM8可抑制LUAD的增殖、迁移和侵袭并诱导其凋亡,而TEM8过表达则产生相反的效果。分子机制研究表明,TEM8主要通过激活Wnt/β-连环蛋白信号通路发挥促进作用。简而言之,我们的研究结果表明,TEM8通过激活Wnt/β-连环蛋白信号通路在LUAD进展中起关键作用,并且可作为LUAD的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8049/8552045/ef91a4bfdf8e/fonc-11-712371-g001.jpg

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