Aberrant sialylation has long been correlated with human
cancer. Increased ST6 Gal I (β-galactoside α 2, 6
sialyltransferase) and consequently higher levels of cell-surface α 2, 6 sialylation has been associated with human
colorectal cancer (CRC)
metastasis. We have extensive circumstantial data that sialylation is connected to
cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in
cancer metastasis. To investigate the molecular mechanism underlying the
ST6Gal I-mediated
metastasis of CRC, we silenced the
ST6Gal I gene in a metastatic SW620 CRC cell line (SW620-shST6Gal I) and examined the metastatic behavior of the cells. We found that various hallmarks of metastatic ability were considerably enhanced in ST6Gal 1-depleted SW620 clones, as assessed both in vitro and in vivo . In particular, the
metastasis suppressor, KAI1, was down-regulated in
ST6Gal I-deficient SW620 clones. This reflected the increased exosome-mediated exportation of KAI1, and was associated with a decrease in the KAI1-mediated inhibition of
integrin. These findings indicate that gene silencing of
ST6Gal I could enhance
metastasis of CRC by down-regulating KAI1 activity and rescuing its negative effects on
integrin signaling.