Altered glycosylation is a common feature of
cancer cells. It takes a variety of forms, which includes loss of expression or excessive expression of some structures, the accumulation of precursors, the appearance of novel structures, etc. Notably, these changes in
glycan structure do not occur as a random consequence of disorder biology. Only a limited subset of
oligosaccharides is found frequently enriched on the
tumor cell surface and implicated in different
tumor phenotypes. Among these, altered sialylation has long been associated with metastatic cell behaviors such as invasion and enhanced cell survival and accumulating evidence points to the alteration occurring in the
sialic acid linkage to other
sugars, which normally exists in three main configurations: α2,3, α2,6, and α2,8, catalyzed by a group of
sialyltransferases. The aberrant expression of all three configurations has been described in
cancer progression. However, the increased α2,6 sialylation catalyzed by β-galactoside α2,6 sialyltranferase 1 (
ST6Gal I) is frequently observed in many types of the
cancers. In this review, we describe the findings on the role of
ST6Gal I in
cancer progression, and highlight in particular the knowledge of how
ST6Gal I-mediated α2,6 sialylated
glycans or sialylated
carrier proteins regulate cell signaling to promote the malignant phenotype of human
carcinoma.