title: Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction.
abstract: 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.
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3].
authors.forename: Dae Gyu
authors.initials: DG
authors.lastname: Kim
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3].
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kwon
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, USA.
authors.forename: Nicolas L
authors.initials: NL
authors.lastname: Young
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Korea University, Sejong, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Korea University, Sejong, Korea.
authors.forename: Ameeq Ul
authors.initials: AU
authors.lastname: Mushtaq
authors.affiliation: College of Pharmacy, Korea University, Sejong, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Han
authors.affiliation: Yuhan Research Institute, Yongin, Korea.
authors.forename: Ho Woong
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Yuhan Research Institute, Yongin, Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Joo
authors.affiliation: Yuhan Research Institute, Yongin, Korea.
authors.forename: Youn
authors.initials: Y
authors.lastname: Hur
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Wonyoung
authors.initials: W
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Heekyoung
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, Korea.
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Kibom
authors.initials: K
authors.lastname: Kim
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kang
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
authors.forename: Youngji
authors.initials: Y
authors.lastname: Moon
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Rhee
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Han
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology and WCU Department of Biomedical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology and WCU Department of Biomedical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Yang
authors.affiliation: BRI, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.affiliation: The National Center for Drug Screening, Zhangjiang High-Tech Park, Shanghai, China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.affiliation: 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3] World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D008250:Lysine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis; D021381:Protein Transport; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017474:Receptors, Laminin; D008250:Lysine-tRNA Ligase