Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction
- Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction
- Dae Gyu Kim; Jin Young Lee; Nam Hoon Kwon; Pengfei Fang; Qian Zhang; Jing Wang; Nicolas L Young; Min Guo; Hye Young Cho; Ameeq Ul Mushtaq; Young Ho Jeon; Jin Woo Choi; Jung Min Han; Ho Woong Kang; Jae Eun Joo; Youn Hur; Wonyoung Kang; Heekyoung Yang; Do-Hyun Nam; Mi-Sook Lee; Jung Weon Lee; Eun-Sook Kim; Aree Moon; Kibom Kim; Doyeun Kim; Eun Joo Kang; Youngji Moon; Kyung Hee Rhee; Byung Woo Han; Jee Sun Yang; Gyoonhee Han; Won Suk Yang; 이철주; Ming-Wei Wang; Sunghoon Kim
- Issue Date
- Nature chemical biology
- VOL 10, NO 1, 29-34
- Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.
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