Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth
Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth
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siRNA 抑制 FUT1/FUT4 表达可抑制肿瘤生长
DOI：
10.1016/j.bbamcr.2007.10.007
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发表时间：
2008-02-01
影响因子：
5.1
通讯作者：
Yan, Qiu
中科院分区：
文献类型：
--
作者：
Zhang, Zhenbo;Sun, Ping;Yan, Qiu
刘易斯Y（LeY）抗原在多种上皮细胞来源的人类癌中高度表达。最近的研究表明，功能性阻断LeY可能为癌症的治疗提供一种新的治疗方法。然而，通过基因操作抑制LeY表达及其对肿瘤细胞增殖的影响尚未研究。我们在这里报告，不同的岩藻糖基转移酶（FUTs）的表达与岩藻糖基转移酶I或IV（FUT 1/4），在人表皮样癌A431细胞合成LeY的两个关键酶的最大表达。应用短干扰RNA技术敲低FUT 1/4表达，可显著降低FUT 1/4和LeY的表达，通过下调表皮生长因子受体（EGFR）信号通路抑制细胞增殖。用FUT 1 siRNA或FUT 4 siRNA处理接种到裸鼠中的A431细胞极大地抑制了肿瘤生长。抑制FUT 1/4的表达也阻断了EGF诱导的EGFR和丝裂原活化蛋白激酶的酪氨酸磷酸化。总之，通过RNAi技术抑制FUT 1/4的表达减少了LeY的合成并抑制了癌症的生长。它可以作为一种潜在的方法用于治疗表达LeY糖缀合物的癌症。(C)2007 Elsevier B. V.保留所有权利。
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. (C) 2007 Elsevier B.V. All rights reserved.