Abstract
The sialyl Lewis a and x (sLea/x) antigens frequently displayed on the surface of tumor cells are involved in metastasis. Their synthesis has been attributed to altered expression of selective glycosyltransferases. Identification of these glycosyltransferases and the glycoproteins that carry these carbohydrate antigens should help advance our understanding of selectin-mediated cancer metastasis. In this study, quantitative real-time polymerase chain reaction analysis coupled with in situ proximity ligation assay and small interference RNA treatment shows involvement of β3galactosyltransferase- V in the synthesis of MUC16-associated sLea in H292 cells. Also, α3fucosyltransferase-V, which is absent in BEAS-2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells, participates in the synthesis of MUC1-associated sLex in CFT1 human immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either enzyme suppresses migration, and selectin tethering and rolling properties of H292 cells under dynamic flow as determined by wound healing and parallel plate flow chamber assays, respectively. These results provide insights into how the synthesis of mucinassociated selectin ligands and the metastatic properties of cancer cells can be regulated by selective glycosyltransferases that work on mucins. They may help develop novel anticancer drugs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 963-975 |
| Number of pages | 13 |
| Journal | Glycobiology |
| Volume | 25 |
| Issue number | 9 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- Cell adhesion
- Glycosylation
- Glycosyltransferases
- Lung cancer
- Metastasis
- Sialyl Lewis antigens
ASJC Scopus subject areas
- Biochemistry
Cite this
Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands. / Chachadi, Vishwanath B.; Bhat, Ganapati; Cheng, Pi-Wan.
In: Glycobiology, Vol. 25, No. 9, 01.01.2015, p. 963-975.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands
AU - Chachadi, Vishwanath B.
AU - Bhat, Ganapati
AU - Cheng, Pi-Wan
PY - 2015/1/1
Y1 - 2015/1/1
N2 - The sialyl Lewis a and x (sLea/x) antigens frequently displayed on the surface of tumor cells are involved in metastasis. Their synthesis has been attributed to altered expression of selective glycosyltransferases. Identification of these glycosyltransferases and the glycoproteins that carry these carbohydrate antigens should help advance our understanding of selectin-mediated cancer metastasis. In this study, quantitative real-time polymerase chain reaction analysis coupled with in situ proximity ligation assay and small interference RNA treatment shows involvement of β3galactosyltransferase- V in the synthesis of MUC16-associated sLea in H292 cells. Also, α3fucosyltransferase-V, which is absent in BEAS-2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells, participates in the synthesis of MUC1-associated sLex in CFT1 human immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either enzyme suppresses migration, and selectin tethering and rolling properties of H292 cells under dynamic flow as determined by wound healing and parallel plate flow chamber assays, respectively. These results provide insights into how the synthesis of mucinassociated selectin ligands and the metastatic properties of cancer cells can be regulated by selective glycosyltransferases that work on mucins. They may help develop novel anticancer drugs.
AB - The sialyl Lewis a and x (sLea/x) antigens frequently displayed on the surface of tumor cells are involved in metastasis. Their synthesis has been attributed to altered expression of selective glycosyltransferases. Identification of these glycosyltransferases and the glycoproteins that carry these carbohydrate antigens should help advance our understanding of selectin-mediated cancer metastasis. In this study, quantitative real-time polymerase chain reaction analysis coupled with in situ proximity ligation assay and small interference RNA treatment shows involvement of β3galactosyltransferase- V in the synthesis of MUC16-associated sLea in H292 cells. Also, α3fucosyltransferase-V, which is absent in BEAS-2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells, participates in the synthesis of MUC1-associated sLex in CFT1 human immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either enzyme suppresses migration, and selectin tethering and rolling properties of H292 cells under dynamic flow as determined by wound healing and parallel plate flow chamber assays, respectively. These results provide insights into how the synthesis of mucinassociated selectin ligands and the metastatic properties of cancer cells can be regulated by selective glycosyltransferases that work on mucins. They may help develop novel anticancer drugs.
KW - Cell adhesion
KW - Glycosylation
KW - Glycosyltransferases
KW - Lung cancer
KW - Metastasis
KW - Sialyl Lewis antigens
UR - http://www.scopus.com/inward/record.url?scp=84943240526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943240526&partnerID=8YFLogxK
U2 - 10.1093/glycob/cwv030
DO - 10.1093/glycob/cwv030
M3 - Article
C2 - 25972125
AN - SCOPUS:84943240526
VL - 25
SP - 963
EP - 975
JO - Glycobiology
JF - Glycobiology
SN - 0959-6658
IS - 9
ER -