Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Biochem Biophys Res Commun. 2022 Jun 30;611:99-106. doi: 10.1016/j.bbrc.2022.04.068. Epub 2022 Apr 20.
In recent years, cancer metabolism has attracted attention as a therapeutic target, and glutamine metabolism is considered one of the most important metabolic processes in cancer. Solute carrier family 1 member 5 (SLC1A5) is a sodium channel that functions as a glutamine transporter. In various cancer types, SLC1A5 gene expression is enhanced, and cancer cell growth is suppressed by inhibition of SLC1A5. However, the involvement of SLC1A5 in clear cell renal cell carcinoma (ccRCC) is unclear. Therefore, in this study, we evaluated the clinical importance of SLC1A5 in ccRCC using The Cancer Genome Atlas database. Our findings confirmed that SLC1A5 was a prognosis factor for poor survival in ccRCC. Furthermore, loss-of-function assays using small interfering RNAs or an SLC1A5 inhibitor (V9302) in human ccRCC cell lines (A498 and Caki1) showed that inhibition of SLC1A5 significantly suppressed tumor growth, invasion, and migration. Additionally, inhibition of SLC1A5 by V9302 in vivo significantly suppressed tumor growth, and the antitumor effects of SLC1A5 inhibition were related to cellular senescence. Our findings may improve our understanding of ccRCC and the development of new treatment strategies for ccRCC.
近年来，癌症代谢已成为治疗靶点之一，而谷氨酰胺代谢被认为是癌症中最重要的代谢过程之一。溶质载体家族 1 成员 5（SLC1A5）是一种作为谷氨酰胺转运体的钠离子通道。在各种癌症类型中，SLC1A5 基因表达增强，抑制 SLC1A5 可抑制癌细胞生长。然而，SLC1A5 在透明细胞肾细胞癌（ccRCC）中的参与尚不清楚。因此，在这项研究中，我们使用癌症基因组图谱数据库评估了 SLC1A5 在 ccRCC 中的临床重要性。我们的研究结果证实，SLC1A5 是 ccRCC 不良生存的预后因素。此外，在人 ccRCC 细胞系（A498 和 Caki1）中使用小干扰 RNA 或 SLC1A5 抑制剂（V9302）进行的功能丧失测定表明，抑制 SLC1A5 可显著抑制肿瘤生长、侵袭和迁移。此外，V9302 在体内抑制 SLC1A5 可显著抑制肿瘤生长，SLC1A5 抑制的抗肿瘤作用与细胞衰老有关。我们的研究结果可能会增进我们对 ccRCC 的理解，并为 ccRCC 的新治疗策略的发展提供依据。
