Claudin 4通过NNAT/Wnt信号通路增强胶质瘤细胞的恶性程度。
Claudin 4 enhances the malignancy of glioma cells via NNAT/Wnt signaling.
作者信息
Yang Feilong, Xu Wuhuan, Tang Xielin, Li Qianke, Hou Xiaolin, Hui Xuhui
机构信息
Department of Neurosurgery, West China Hospital, Sichuan University Chengdu, Sichuan, China.
Department of Neurosurgery, The Affiliated Santai Hospital of North Sichuan Medical College Mianyang, Sichuan, China.
出版信息
Am J Cancer Res. 2023 Jun 15;13(6):2530-2539. eCollection 2023.
Gliomas are the most common malignancies of the central nervous system and are associated with high mortality rates. However, the pathogenesis of gliomas is unclear. In this study, we show that elevated claudin-4 (CLDN4) levels in glioma tissues are associated with poor clinical outcomes. We found that upregulating the expression of CLND4 enhanced the proliferative and migratory capacities of glioma cells. Mechanistically, CLND4 upregulated Neuronatin (NNAT) by activating Wnt3A signaling, and aided in the progression of the glioma. Most importantly, our data demonstrated that CLND4 overexpression caused rapid tumor growth in mice injected with LN229 cells and reduced the survival of these mice. Our findings reveal that CLND4 modulates malignancy in glioma cells; targeting CLDN4 may open up new avenues for glioma treatment.
神经胶质瘤是中枢神经系统最常见的恶性肿瘤，且死亡率很高。然而，神经胶质瘤的发病机制尚不清楚。在本研究中，我们发现神经胶质瘤组织中紧密连接蛋白4（CLDN4）水平升高与不良临床预后相关。我们发现上调CLND4的表达可增强神经胶质瘤细胞的增殖和迁移能力。从机制上讲，CLND4通过激活Wnt3A信号上调神经调节素（NNAT），并促进神经胶质瘤的进展。最重要的是，我们的数据表明，CLND4过表达导致注射LN229细胞的小鼠肿瘤快速生长，并缩短了这些小鼠的生存期。我们的研究结果表明，CLND4调节神经胶质瘤细胞的恶性程度；靶向CLDN4可能为神经胶质瘤治疗开辟新途径。
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