Abstract
Lewis Y (LeY) antigen is highly expressed in a variety of human carcinomas of epithelial cell origin. Recent studies suggest functional blockade of LeY may provide a novel therapeutic approach for the treatment of cancers. However, suppressing LeY expression by genetic manipulation and its impact on neoplastic cell proliferation has not been investigated. We report here that different fucosyltransferases (FUTs) were expressed with the greatest expression of fucosyltransferase I or IV (FUT1/4), the two key enzymes for the synthesis of LeY in human epidermoid carcinoma A431 cells. Knocking down FUT1/4 expression by short interfering RNA technique dramatically reduced the expression of FUT1/4 and LeY and inhibited cell proliferation through decreasing epidermal growth factor receptor (EGFR) signaling pathway. Treatment of A431 cells that were inoculated into the nude mice with FUT1 siRNA or FUT4 siRNA greatly impeded tumor growth. Suppressing FUT1/4 expression also blocked EGF-induced tyrosine phosphorylation of EGFR and mitogen-activated protein kinases. In conclusion, suppressing the expression of FUT1/4 by RNAi technology reduces the synthesis of LeY and inhibits cancer growth. It may serve as a potential methodology for the treatment of cancers that express LeY glycoconjugates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 287-296 |
| Number of pages | 10 |
| Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
| Volume | 1783 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2008 |
| Externally published | Yes |
Funding
Grant support: National Natural Science Foundation of China Research grants (30270329, 30670465 and 30672753) and Liaoning Provincial Core Lab of Glycobiology and Glycoengineering grant.
Keywords
- Fucosyltransferase
- Lewis antigen
- Tumor growth
- siRNA
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
