Chemical inhibition of prometastatic lysyl-tRNA synthetase–laminin receptor interaction
作者： Dae Gyu Kim , Jin Young Lee , Nam Hoon Kwon , Pengfei Fang , Qian Zhang
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摘要: Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to plasma membrane after laminin signal and stabilizes 67-kDa receptor (67LR) that is implicated cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found small compound BC-K-YH16899, which binds KRS, impinged on interaction of KRS with 67LR suppressed metastasis three different mouse models. The inhibited KRS-67LR two ways. First, it directly blocked association between 67LR. Second, dynamic movement N-terminal extension reduced localization KRS. However, did affect catalytic activity Our results suggest specific modulation cancer-related may offer way control while avoiding toxicities associated inhibition normal functions
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