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Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses pancreatic cancer cell migration

Authors
 Seung Jae Jeong  ;  Jong Hyun Kim  ;  Beom Jin Lim  ;  Ina Yoon  ;  Ji-Ae Song  ;  Hee-sun Moon  ;  Doyeun Kim  ;  Dong Ki Lee  ;  Sunghoon Kim 
Citation
 Experimental and Molecular Medicine, Vol.50(1) : e424, 2018 
Journal Title
 Experimental and Molecular Medicine 
ISSN
 1226-3613 
Issue Date
2018
Abstract
Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers. In this study, data provided suggests that threonine starvation reduces the level of MUC1 and inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly, knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a positive correlation between TRS and MUC1 levels is observed in human pancreatic cancer cells. Concurrent with these results, the bioinformatics data indicate that co-expression of both TRS and MUC1 is correlated with the poor survival of pancreatic cancer patients. Taken together, these findings suggest a role for TRS in controlling MUC1-mediated cancer cell migration and provide insight into targeting TRS as a novel therapeutic approach to pancreatic cancer treatment
Files in This Item:
T201803840.pdf Download
DOI
10.1038/emm.2017.231
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
이동기(Lee, Dong Ki) ORCID logo https://orcid.org/0000-0002-0048-9112
임범진(Lim, Beom Jin) ORCID logo https://orcid.org/0000-0003-2856-0133
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165319
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