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.