alpha2,6-hyposialylation of c-Met abolishes cell motility of ST6Gal-I-knockdown HCT116 cells.

Acta Pharmacol Sin. 2009 Jun 1; Qian J, Zhu CH, Tang S, Shen AJ, Ai J, Li J, Geng MY, Ding JAim:We aimed to investigate the potential modification of previously unrecognized surface glycoprotein(s) by alpha2,6-sialylation other than by integrins.Methods:The expression of beta-galactoside alpha2,6-sialyltransferase (ST6Gal-I) in the colon cancer cell line HCT116 was reduced by siRNA. The adhesion and Boyden chamber assay were used to detect the variation in cell motility. alpha2,6-Sialylation proteins were detected with lectin affinity assay. The mRNA expression, protein expression and downstream signaling modulation with siRNA were detected using reverse transcription-polymerase chain reaction, flow cytometry analysis, and Western blot.Results:In HCT116 cells, the knockdown of ST6Gal-I inhibited cell motility, but did not affect cell adhesion. This selectively altered cell migration was caused by the loss of alpha2,6-sialic acid structures on c-Met. Moreover, STAT3 was dephosphorylated at tyrosine 705 in ST6Gal-I-knockdown (ST6Gal-I-KD) HCT116 cells.Conclusion:c-Met is the substrate of ST6Gal-I. The hyposialylation of c-Met can abolish cell motility in ST6Gal-I-KD HCT116 cells.Acta Pharmacologica Sinica advance online publication, 1 June 2009; doi: 10.1038/aps.2009.84.