Sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) glycans are expressed on 
highly metastatic colon cancer cells. They promote extravasation of cancer cells 
and tumor angiogenesis via interacting with E-selectin on endothelial cells. 
Recently, epithelial-mesenchymal transition (EMT) has been noted as a critical 
phenotypic alteration in metastatic cancer cells. To address the association 
between sLe(x/a) expression and EMT, we assessed whether sLe(x/a) are highly 
expressed on colon cancer cells undergoing EMT. Treatment of HT29 and DLD-1 
cells with EGF and/or basic FGF (bFGF) induced EMT and significantly increased 
sLe(x/a) expression resulting in enhanced E-selectin binding activity. The 
transcript levels of the glycosyltransferase genes ST3GAL1/3/4 and FUT3 were 
significantly elevated and that of FUT2 was significantly suppressed by the 
treatment. We provide evidence that ST3GAL1/3/4 and FUT3 are transcriptionally 
up-regulated by c-Myc with probable involvement of Ser62 phosphorylation, and 
that FUT2 is transcriptionally down-regulated through the attenuation of CDX2. 
The contribution of c-Myc and CDX2 to the sLe(x/a) induction was proved to be 
significant by knockdown or forced expression experiments. Interestingly, the 
cells undergoing EMT exhibited significantly increased VEGF secretion, which can 
promote tumor angiogenesis in cooperation with sLe(x/a). Finally, 
immunohistological study indicated high E-selectin ligand expression on cancer 
cells undergoing EMT in vivo, supporting their coexistence observed in vitro. 
These results suggest a significant link between sLe(x/a) expression and EMT in 
colon cancer cells and a pivotal role of c-Myc and CDX2 in regulating sLe(x/a) 
expression during EMT.