Department of Hematologic and Oncology, Xinjiang Clinical Research Center for Precision Medicine of Digestive System Tumor, the Center Hospital of Karamay City, Karamay 834000, China.
Department of Oncology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):716-724. doi: 10.3724/abbs.2022048.
Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of c-Myc to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.
食管鳞状细胞癌（ESCC）是一种常见的食管癌亚型，发病率较高。手术仍然是早期 ESCC 的主要治疗策略。然而，治疗效果并不理想。因此，寻找新的治疗方法非常重要。在本研究中，我们测量了临床样本中 NEDD4L 的水平，NEDD4L 是一种泛素蛋白连接酶，并通过 CCK-8 测定、流式细胞术和生化分析分别研究了 NEDD4L 对 TE14 细胞活力、细胞周期进程和谷氨酰胺代谢的影响。结果表明，NEDD4L 在 ESCC 标本中显著降低，其表达降低与不良的临床结局相关。NEDD4L 的过表达显著抑制 TE14 细胞的活力、细胞周期进程和谷氨酰胺代谢。机制研究表明，NEDD4L 通过泛素化 c-Myc 调节肿瘤进展，并调节谷氨酰胺代谢。NEDD4L 通过泛素化 c-Myc 降低 GLS1 和 SLC1A5 的表达，从而抑制 ESCC 中的细胞活力、细胞周期进程和谷氨酰胺代谢。我们的研究结果强调了 NEDD4L/c-Myc 信号通路在 ESCC 中的重要性。
