Inhibition of muc1 biosynthesis via threonyl-trna synthetase suppresses pancreatic cancer cell migration

Seung Jae Jeong, Jong Hyun Kim, Beom Jin Lim, Ina Yoon, Ji Ae Song, Hee Sun Moon, Doyeun Kim, Dong Ki Lee, Sunghoon Kim

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Article numbere424
JournalExperimental and Molecular Medicine
Issue number1
Publication statusPublished - 2018

Bibliographical note

Funding Information:
This work was supported by a Global Frontier Project grant (NRF-M3A6A4-2010-0029785) of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.

Publisher Copyright:
© The Author(s) 2018.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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