Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Environ Toxicol. 2020 Dec;35(12):1299-1307. doi: 10.1002/tox.22994. Epub 2020 Jul 11.
Recent evidences show that acylglycerol kinase (AGK) expression is related to the occurrence and development of various human cancers. However, its roles in nasopharyngeal carcinoma (NPC) progression are still unclear. This work aims to explore the roles of AGK in NPC cell stemness. It was shown that AGK expression was higher in NPC tissues compared to the adjacent tissues. Online dataset analysis revealed that AGK expression was negatively correlated with the overall survival of NPC patients. Gain and loss of functional experiments demonstrated that AGK positively regulated the stemness of NPC cells, as evident by the change of the tumor sphere-formation ability, ALDH1 activity and expression of stemness critical regulators. KEGG analysis were performed to determine the potential pathways of AGK involved in NPC cell stemness and showed that the PI3K/Akt pathway exhibited the most correlation with AGK expression. Further mechanistic studies confirmed that AGK promoted the stemness of NPC cells through activating the PI3K/Akt pathway, and thus enhancing β-catenin accumulation in nucleus. This study demonstrates a novel AGK/PI3K/Akt/β-catenin axis involving in NPC cell stemness.
最近的证据表明，酰基甘油激酶 (AGK) 的表达与各种人类癌症的发生和发展有关。然而，其在鼻咽癌 (NPC) 进展中的作用尚不清楚。本研究旨在探讨 AGK 在 NPC 细胞干性中的作用。结果表明，AGK 在 NPC 组织中的表达高于相邻组织。在线数据集分析显示，AGK 的表达与 NPC 患者的总生存率呈负相关。功能获得和缺失实验表明，AGK 可正向调节 NPC 细胞的干性，其表现在肿瘤球形成能力、ALDH1 活性和干性关键调控因子的表达变化上。进行了 KEGG 分析以确定 AGK 参与 NPC 细胞干性的潜在途径，结果表明 PI3K/Akt 途径与 AGK 表达相关性最强。进一步的机制研究证实，AGK 通过激活 PI3K/Akt 通路促进 NPC 细胞干性，从而增加细胞核内β-catenin 的积累。本研究证明了一个涉及 NPC 细胞干性的新型 AGK/PI3K/Akt/β-catenin 轴。
