Kim, Dae Gyu Lee, Jin Young Kwon, Nam Hoon Fang, Pengfei Zhang, Qian Wang, Jing Young, Nicolas L. Guo, Min Cho, Hye Young Mushtaq, Ameeq Ul Jeon, Young Ho Choi, Jin Woo Han, Jung Min Kang, Ho Woong Joo, Jae Eun Hur, Youn Kang, Wonyoung Yang, Heekyoung Nam, Do-Hyun Lee, Mi-Sook Lee, Jung Weon Kim, Eun-Sook Moon, Aree Kim, Kibom Kim, Doyeun Kang, Eun Joo Moon, Youngji Rhee, Kyung Hee Han, Byung Woo Yang, Jee Sun Han, Gyoonhee Yang, Won Suk Lee, Cheolju Wang, Ming-Wei Kim, Sunghoon 2024-01-20T10:34:22Z 2024-01-20T10:34:22Z 2021-09-05 2014-01 1552-4450 https://pubs.kist.re.kr/handle/201004/127253 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. English NATURE PUBLISHING GROUP ION-CYCLOTRON RESONANCE MASS-SPECTROMETRY SCATTERING SAXS GENE-EXPRESSION CELL INVASION SYSTEM CANCER METASTASIS CARCINOMA PROTEINS Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction Article 10.1038/NCHEMBIO.1381 1 NATURE CHEMICAL BIOLOGY, v.10, no.1, pp.29 - U57 NATURE CHEMICAL BIOLOGY 10 1 29 U57 scie scopus 000328854900007 2-s2.0-84891006164 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article ION-CYCLOTRON RESONANCE MASS-SPECTROMETRY SCATTERING SAXS GENE-EXPRESSION CELL INVASION SYSTEM CANCER METASTASIS CARCINOMA PROTEINS