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.