Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells
Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells
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DOI：
10.1111/j.1349-7006.2009.01125.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Taniguchi, Naoyuki
中科院分区：
文献类型：
--
作者：
Osumi, Daisuke;Takahashi, Motoko;Taniguchi, Naoyuki
α 1，6-岩藻糖基转移酶（Fut 8）是一种催化α 1，6核心岩藻糖引入N-聚糖最内部N-乙酰葡糖胺残基的酶，与发育、免疫系统和肿瘤发生有关。我们发现α 1，6-岩藻糖基转移酶和E-钙粘蛋白的表达水平在原发性结直肠癌样本中显著升高。有趣的是，低分子量群体的E-钙粘蛋白出现以及正常大小的E-钙粘蛋白在癌症样品中。为了研究α 1，6-岩藻糖基转移酶和E-钙粘蛋白表达之间的相关性，我们将α 1，6-岩藻糖基转移酶引入WiDr人结肠癌细胞中。结果表明，在密集培养中，在α 1，6-岩藻糖基转移酶转染的WiDr细胞中E-钙粘蛋白的低分子量群体显著增加，这导致细胞-细胞粘附的增强。无酶活性的突变α 1，6-岩藻糖基转移酶的转染对E-钙粘蛋白表达没有影响，表明核心岩藻糖基化参与了该现象。在α 1，6-岩藻糖基转移酶敲除的小鼠胰腺腺泡细胞癌TGP 49细胞中，E-cadherin的表达和E-cadherin依赖的细胞-细胞粘附减少。将α 1，6-岩藻糖基转移酶引入α 1，6-岩藻糖基转移酶（-/-）小鼠的肾上皮细胞中，恢复了E-钙粘蛋白和E-钙粘蛋白依赖性细胞-细胞粘附的表达。基于凝集素印迹、肽N-糖苷酶F处理和脉冲追踪研究的结果，证明E-钙粘蛋白的低分子量群体含有肽N-糖苷酶F不敏感的糖链，并且在α 1，6-岩藻糖基转移酶转染子中E-钙粘蛋白的周转率降低。因此，表明核心岩藻糖基化调节寡糖的加工和E-钙粘蛋白的周转。这些结果表明核心岩藻糖基化在癌症中细胞-细胞粘附的调节中可能起作用。（Cancer Sci 2009; 100：888-896）。
alpha 1,6-Fucosyltransferase (Fut8), an enzyme that catalyzes the introduction of alpha 1,6 core fucose to the innermost N-acetylglucosamine residue of the N-glycan, has been implicated in the development, immune system, and tumorigenesis. We found that alpha 1,6-fucosyltransferase and E-cadherin expression levels are significantly elevated in primary colorectal cancer samples. Interestingly, low molecular weight population of E-cadherin appeared as well as normal sized E-cadherin in cancer samples. To investigate the correlation between alpha 1,6-fucosyltransferase and E-cadherin expression, we introduced alpha 1,6-fucosyltransferase in WiDr human colon carcinoma cells. It was revealed that the low molecular weight population of E-cadherin was significantly increased in alpha 1,6-fucosyltransferase-transfected WiDr cells in dense culture, which resulted in an enhancement in cell-cell adhesion. The transfection of mutated alpha 1,6-fucosyltransferase with no enzymatic activity had no effect on E-cadherin expression, indicating that core fucosylation is involved in the phenomena. In alpha 1,6-fucosyltransferase knock down mouse pancreatic acinar cell carcinoma TGP49 cells, the expression of E-cadherin and E-cadherin dependent cell-cell adhesion was decreased. The introduction of alpha 1,6-fucosyltransferase into kidney epithelial cells from alpha 1,6-fucosyltransferase (-/-) mice restored the expression of E-cadherin and E-cadherin-dependent cell-cell adhesion. Based on the results of lectin blotting, peptide N-glycosidase F treatment, and pulse-chase studies, it was demonstrated that the low molecular weight population of E-cadherin contains peptide N-glycosidase F insensitive sugar chains, and the turnover rate of E-cadherin was reduced in alpha 1,6-Fucosyltransferase transfectants. Thus, it was suggested that core fucosylation regulates the processing of oligosaccharides and turnover of E-cadherin. These results suggest a possible role of core fucosylation in the regulation of cell-cell adhesion in cancer. (Cancer Sci 2009; 100: 888-896).