TY - JOUR
T1 - 5-Aza-2′-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene
AU - Chachadi, Vishwanath B.
AU - Cheng, Helen
AU - Klinkebiel, David
AU - Christman, Judith K.
AU - Cheng, Pi Wan
N1 - Funding Information:
The work was supported by research grants from the following sources: NIH 2RO1HL48282, R21HL097238, Nebraska Research Initiative-Cancer Glycobiology Program, and Nebraska Tobacco Smoking Research LB506. We also acknowledge the glycogene microarray analysis provided by the Core G of The Consortium for Functional Glycomics funded by NIGMS – GM62116.
PY - 2011/4
Y1 - 2011/4
N2 - Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced cancers. However, the mechanism for the production of this cancer antigen is not entirely clear. The objective of this study is to examine whether epigenetics is involved in the regulation of the formation of this antigen. We observed an increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with 5-Aza-2′-deoxycytidine. This treatment enhanced the expression of β-galactoside:α2,3-sialyltransferase 6 gene and sialyl Lewis X on MUC1, and the adherence of these cells to E-selectin under dynamic flow conditions. In addition, 5-Aza-2′-deoxycytidine treatment inhibited methylation of β-galactoside:α2,3-sialyltransferase 6 gene and siRNA knockdown of this gene drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude that 5-Aza-2′-deoxycytidine treatment increases sialyl Lewis X on MUC1 by stimulating the β-galactoside:α2,3- sialyltransferase 6 gene via inhibition of DNA methylation. Increased sialyl Lewis X by 5-Aza-2′-deoxycytidine raises a concern about the safety of this chemotherapeutic drug. In addition, β-galactoside:α2,3- sialyltransferase 6 gene may be a potential therapeutic target for suppressing tumorigenicity of colon cancer.
AB - Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced cancers. However, the mechanism for the production of this cancer antigen is not entirely clear. The objective of this study is to examine whether epigenetics is involved in the regulation of the formation of this antigen. We observed an increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with 5-Aza-2′-deoxycytidine. This treatment enhanced the expression of β-galactoside:α2,3-sialyltransferase 6 gene and sialyl Lewis X on MUC1, and the adherence of these cells to E-selectin under dynamic flow conditions. In addition, 5-Aza-2′-deoxycytidine treatment inhibited methylation of β-galactoside:α2,3-sialyltransferase 6 gene and siRNA knockdown of this gene drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude that 5-Aza-2′-deoxycytidine treatment increases sialyl Lewis X on MUC1 by stimulating the β-galactoside:α2,3- sialyltransferase 6 gene via inhibition of DNA methylation. Increased sialyl Lewis X by 5-Aza-2′-deoxycytidine raises a concern about the safety of this chemotherapeutic drug. In addition, β-galactoside:α2,3- sialyltransferase 6 gene may be a potential therapeutic target for suppressing tumorigenicity of colon cancer.
KW - 5-Aza-2′- deoxycytidine
KW - Cancer metastasis
KW - Epigenetic regulation of glycosyltransferase gene expression
KW - Mucin biosynthesis
KW - sLe
UR - http://www.scopus.com/inward/record.url?scp=79952101146&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952101146&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2010.12.015
DO - 10.1016/j.biocel.2010.12.015
M3 - Article
C2 - 21168523
AN - SCOPUS:79952101146
SN - 1357-2725
VL - 43
SP - 586
EP - 593
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 4
ER -