Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth

Zhenbo Zhang, Ping Sun, Jiwei Liu, Li Fu, Jie Yan, Yuejian Liu, Lihua Yu, Xiaoqi Wang, Qiu Yan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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 languageEnglish (US)
Pages (from-to)287-296
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Fucosyltransferase
  • Lewis antigen
  • Tumor growth
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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