title: Suppression of lysyl-tRNA synthetase, KRS, causes incomplete epithelial-mesenchymal transition and ineffective cell‑extracellular matrix adhesion for migration.
abstract: The cell-adhesion properties of cancer cells can be targeted to block cancer metastasis. Although cytosolic lysyl-tRNA synthetase (KRS) functions in protein synthesis, KRS on the plasma membrane is involved in cancer metastasis. We hypothesized that KRS is involved in cell adhesion-related 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.
authors.affiliation: Interdisciplinary Program in Genetic Engineering, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Seo Hee
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Dae Gyu
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kwon
authors.affiliation: Interdisciplinary Program in Genetic Engineering, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Genetic Engineering, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000235:genetics*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D008250:Lysine-tRNA Ligase / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; C000613080:KARS1 protein, human; D008250:Lysine-tRNA Ligase