RRC ID 71794
Author Lu J, Isaji T, Im S, Fukuda T, Hashii N, Takakura D, Kawasaki N, Gu J.
Title β-Galactoside α2,6-sialyltranferase 1 promotes transforming growth factor-β-mediated epithelial-mesenchymal transition.
Journal J Biol Chem
Abstract β-Galactoside α2,6-sialyltranferase 1 (ST6GAL1) catalyzes the addition of terminal α2,6-sialylation to N-glycans. Increased expression of ST6GAL1 has been reported in diverse carcinomas and highly correlates with tumor progression. Here, we report that St6gal1 transcription and α2,6-sialylated N-glycans are up-regulated during TGF-β-induced epithelial-mesenchymal transition (EMT) in GE11 cells, requiring the Sp1 element within the St6gal1 promoter. Knockdown of St6gal1 strongly suppressed TGF-β-induced EMT with a concomitant increase in E-cadherin expression, a major determinant of epithelial cell adherens junctions. Conversely, overexpression of ST6GAL1 increased the turnover of cell surface E-cadherin and promoted TGF-β-induced EMT. Overexpressing β-galactoside α2,3-sialyltranferase 4 had little influence on EMT, indicating specificity for α2,6-sialylation. The basal mesenchymal phenotype of MDA-MB-231 human breast cancer cells was partially reversed by ST6GAL1 silencing. Moreover, ST6GAL1 knockdown inhibited the phosphorylation of Akt, but not Smad2, suggesting that ST6GAL1 contributes to EMT through a non-Smad signaling pathway. Taken together, our data indicate that ST6GAL1 promotes TGF-β-dependent EMT as well as maintenance of the mesenchymal state by growth signaling, providing a plausible mechanism whereby up-regulated ST6GAL1 may promote malignant progression.
Volume 289(50)
Pages 34627-41
Published 2014-12-12
DOI 10.1074/jbc.M114.593392
PII S0021-9258(19)56120-8
PMID 25344606
PMC PMC4263869
MeSH Antigens, CD / genetics Antigens, CD / metabolism* Binding Sites Breast Neoplasms / pathology Cadherins / metabolism Cell Line, Tumor Cell Movement / drug effects Disease Progression Epithelial-Mesenchymal Transition / drug effects* Gene Knockdown Techniques Gene Silencing Humans Phenotype Promoter Regions, Genetic / genetics Sialyltransferases / deficiency Sialyltransferases / genetics Sialyltransferases / metabolism* Sp1 Transcription Factor / metabolism Transcriptional Activation / drug effects Transforming Growth Factor beta / pharmacology* Up-Regulation / drug effects
IF 4.238
Human and Animal Cells 293T(RCB22020)