Suppression of lysyl-tRNA synthetase, KRS, causes incomplete epithelial-mesenchymal transition and ineffective cell-extracellular matrix adhesion for migration

Seo Hee Nam, Minkyung Kang, Jihye Ryu, Hye Jin Kim, Doyeun Kim, Dae Gyu Kim, Nam Hoon Kwon, Sunghoon Kim, Jung Weon Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The cell-adhesion properties of cancer cells can be targeted to block cancer metastasis. Although cytosolic lysyltRNA synthetase (KRS) functions in protein synthesis, KRS on the plasma membrane is involved in cancer metastasis. We hypothesized that KRS is involved in cell adhesionrelated signal transduction for cellular migration. To test this hypothesis, colon cancer cells with modulated KRS protein levels were analyzed for cell-cell contact and cell-substrate adhesion properties and cellular behavior. Although KRS suppression decreased expression of cell-cell adhesion molecules, cells still formed colonies without being scattered, supporting an incomplete epithelial mesenchymal transition. Noteworthy, KRS-suppressed cells still exhibited focal adhesions on laminin, with Tyr397-phopshorylated focal adhesion kinase (FAK), but they lacked laminin-adhesion-mediated extracellular signal-regulated kinase (ERK) and paxillin activation. KRS, p67LR and integrin α6β1 were found to interact, presumably to activate ERK for paxillin expression and Tyr118 phosphorylation even without involvement of FAK, so that specific inhibition of ERK or KRS in parental HCT116 cells blocked cell-cell adhesion and cell-substrate properties for focal adhesion formation and signaling activity. Together, these results indicate that KRS can promote cell-cell and cell- ECM adhesion for migration.

Original languageEnglish
Pages (from-to)1553-1560
Number of pages8
JournalInternational journal of oncology
Volume48
Issue number4
DOIs
Publication statusPublished - 2016 Apr

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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