アミノ酸トランスポーターLAT1はカバジタキセル耐性前立腺癌細胞においてCDK1とCDK2を介して細胞増殖に寄与する

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-081
• Main Authors: 新井, 隆之, 斎藤, 心平, 安西, 尚彦, 坂本, 信一, 溝上, 敦, 梨井, 隼菱, 金井, 好克, 市川, 智彦
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: cancer; prostate; transporter
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_1-B-P-081

Background: L-type amino acid transporter 1 (LAT1) is known to be highly expressed in various cancer types. We explored the role of LAT1 in cabazitaxel-resistant prostate cancer cells using phosphoproteome analysis.Materials and Methods: We used PC-3, and a cabazitaxel-resistant strain generated based on PC-3 (PC-3-TxR/CxR). JPH203, a specific inhibitor of LAT1, was used to inhibit LAT1 function. Phosphoproteome analysis was used to quantitatively investigate the proteins and sites of phosphorylation that are altered by JPH203 administration.Results: Compared to PC-3, LAT1 expression was significantly upregulated in PC-3-TxR/CxR. JPH203 significantly inhibited the migration and invasion of PC-3-TxR/CxR cell. Phosphoproteome analysis showed that JPH203 treatment reduced the activity of CDK1 and CDK2 as kinases more than previously known mTOR in PC-3-TxR/CxR cell. The decrease of phosphorylation in Cdc6 and Rb, substrates of CDK1 and CDK2, respectively, by treatment with JPH203 was confirmed by Western blotting.Conclusions: Current date may indicate that LAT1 has a crucial role to progression of cabazitaxel-resistant prostate cancer via CDK1 and CDK2.