Dynamic sialylation in Transforming Growth Factor-{beta}-induced epithelial to mesenchymal transition [Glycobiology and Extracellular Matrices]
March 25th, 2015 by Du, J., Hong, S., Dong, L., Cheng, B., Lin, L., Zhao, B., Chen, Y.-G., Chen, X.
Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and organ formation. Aberrant regulation of EMT often leads to tumor progression. Changes in cell-surface sialylation have recently been implicated in mediating EMT. Herein we report the visualization of dynamic changes of sialylation and glycoproteomic analysis of newly synthesized sialylated proteins in EMT by metabolic labeling of sialylated glycans with azides, followed by click-labeling with fluorophores and affinity tags. We discovered that sialylation was downregulated during EMT, but then reverted and upregulated in the mesenchymal state after EMT, accompanied by mRNA expression level changes of genes involved in the sialic acid biosynthesis. Quantitative proteomic analysis identified a list of sialylated proteins whose biosynthesis was dynamically regulated during EMT. Sialylation of cell-surface adherent receptor integrin β4 was found to be downregulated, which may regulate integrin functions during EMT. Furthermore, a global sialylation inhibitor was used to probe the functional role of sialylation during EMT. We found that inhibition of sialylation promoted EMT. Taken together, our findings suggest the important role of sialylation in regulating EMT and imply its possible function in related pathophysiological events, such as cancer metastasis.