Department of Digestive System, The First Affiliated Hospital of Jinzhou Medical University, 2 Section 5, Renmin Street, Guta District, Jinzhou City, Liaoning Province, China.
Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, 2 Section 5, Renmin Street, Guta District, Jinzhou City, Liaoning Province, China.
J Biochem Mol Toxicol. 2024 Oct;38(10):e23853. doi: 10.1002/jbt.23853.
Eph receptor B2 (EPHB2) is overexpressed in some tumors and relevant to unfavorable outcomes of tumor patients. By searching Gene Expression Profiling Interactive Analysis and KM Plot websites, we discovered that EPHB2 was highly expressed in patients with esophageal cancer, leading to poor prognosis. However, the role and molecular mechanism of EPHB2 in esophagus cancer is unknown. Our study aims to unveil the underlying mechanism by which EPHB2 modulates the biological properties of esophagus cancer cells. After si-EPHB2 transfection, the malignant biological properties of esophagus cancer cells were determined by several biological experiments. IWP-4 was applied to block Wnt/β-catenin signaling pathway. The expressions of autophagy and Wnt/β-catenin signaling pathway relevant molecules were tested by western blot assay. An increased expression of EPHB2 was happened in esophagus cancer samples and loss of EPHB2 diminished esophagus cancer cells proliferation, migration, and invasion. Moreover, our data showed that depletion of EPHB2 blocked the autophagy and in-activated Wnt/β-catenin signaling pathway in esophagus cancer cells. While, IWP-4 treatment inhibited the autophagy and limited esophagus cancer cells proliferation, migration, and invasion. Moreover, EPHB2 knocked down strengthened the effect of IWP-4 treatment in regulating esophagus cancer cells proliferation, migration, and invasion. Finally, we illustrated that EPHB2 regulated the biological properties of esophagus cancer cells by modulating autophagy and Wnt/β-catenin signaling pathway. Our study illustrated that EPHB2 might be a worthwhile target considering for the treatment of esophagus cancer.
Eph 受体 B2 (EPHB2) 在一些肿瘤中过表达，与肿瘤患者的不良预后相关。通过搜索基因表达谱分析交互分析和 KM 绘图网站，我们发现 EPHB2 在食管癌患者中高表达，导致预后不良。然而，EPHB2 在食管癌中的作用和分子机制尚不清楚。我们的研究旨在揭示 EPHB2 调节食管癌细胞生物学特性的潜在机制。通过 si-EPHB2 转染后，通过几种生物学实验来确定食管癌细胞的恶性生物学特性。应用 IWP-4 阻断 Wnt/β-catenin 信号通路。通过 Western blot 检测自噬和 Wnt/β-catenin 信号通路相关分子的表达。食管癌样本中 EPHB2 的表达增加，而 EPHB2 的缺失则减弱了食管癌细胞的增殖、迁移和侵袭能力。此外，我们的数据表明，EPHB2 的耗竭阻断了食管癌细胞中的自噬和失活的 Wnt/β-catenin 信号通路。而 IWP-4 处理抑制了自噬并限制了食管癌细胞的增殖、迁移和侵袭。此外，EPHB2 敲低增强了 IWP-4 处理在调节食管癌细胞增殖、迁移和侵袭方面的作用。最后，我们阐明了 EPHB2 通过调节自噬和 Wnt/β-catenin 信号通路来调节食管癌细胞的生物学特性。我们的研究表明，EPHB2 可能是治疗食管癌的一个有价值的靶点。
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