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EphA8通过AKT信号传导抑制细胞凋亡,并与乳腺癌的不良预后相关。

EphA8 inhibits cell apoptosis via AKT signaling and is associated with poor prognosis in breast cancer.

作者信息

Wang Gui-Hua, Ni Kan, Gu Changjiang, Huang Jianfei, Chen Jing, Wang Xu-Dong, Ni Qichao

机构信息

Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

出版信息

Oncol Rep. 2021 Aug;46(2). doi: 10.3892/or.2021.8134. Epub 2021 Jul 19.

DOI:10.3892/or.2021.8134
PMID:34278497
Abstract

Erythropoietin‑producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both and . The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl‑2 expression levels and upregulation of p53, Caspase‑3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.

摘要

促红细胞生成素产生肝细胞受体(Ephs)构成受体酪氨酸激酶的最大亚家族,据报道其参与多种生物细胞过程,包括肿瘤发生和癌症进展。本研究旨在通过组织芯片免疫组化分析确定EphA8在乳腺癌(BC)中的表达水平及其临床病理意义。本研究结果显示,EphA8在BC组织中的表达水平上调,且与肿瘤大小和TNM分期相关。此外,EphA8表达水平上调被确定为BC患者预后不良的生物标志物。使用短发夹RNA敲低EphA8表达导致BC细胞凋亡水平增加,增殖、迁移和侵袭能力降低。敲低EphA8还降低了AKT的磷酸化,同时伴随着Bcl-2表达水平下调以及p53、Caspase-3和Bax表达水平上调。此外,敲低EphA8表达增加了BC细胞对紫杉醇的化疗敏感性。总之,本研究结果表明EphA8可能是BC中一个有用的预后标志物,敲低EphA8可能代表一种辅助化疗治疗BC的新策略。

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Comprehensive analysis of Epha10 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in non-small cell lung cancer.全面分析 EphA10 作为非小细胞肺癌临床预后和免疫检查点治疗疗效的预测因子。
Sci Rep. 2024 Aug 23;14(1):19623. doi: 10.1038/s41598-024-70466-8.
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Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor-ligand pairs.前列腺癌细胞-血小板双向信号通过不同的受体-配体对促进钙动员、侵袭和抗凋亡。
Sci Rep. 2023 Feb 17;13(1):2864. doi: 10.1038/s41598-023-29450-x.
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EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma.
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