Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction

Title
Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction
Authors
Dae Gyu KimJin Young LeeNam Hoon KwonPengfei FangQian ZhangJing WangNicolas L YoungMin GuoHye Young ChoAmeeq Ul MushtaqYoung Ho JeonJin Woo ChoiJung Min HanHo Woong KangJae Eun JooYoun HurWonyoung KangHeekyoung YangDo-Hyun NamMi-Sook LeeJung Weon LeeEun-Sook KimAree MoonKibom KimDoyeun KimEun Joo KangYoungji MoonKyung Hee RheeByung Woo HanJee Sun YangGyoonhee HanWon Suk Yang이철주Ming-Wei WangSunghoon Kim
Issue Date
2014-01
Publisher
Nature chemical biology
Citation
VOL 10, NO 1, 29-34
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.
URI
http://pubs.kist.re.kr/handle/201004/50222
ISSN
15524469
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