Fucosylated TGF-β receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.
Fucosylated TGF-β receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.
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DOI：
10.1038/bjc.2013.699
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发表时间：
2014-01-07
影响因子：
8.8
通讯作者：
Kato, J.
中科院分区：
文献类型：
--
作者：
Hirakawa, M.;Takimoto, R.;Tamura, F.;Yoshida, M.;Ono, M.;Murase, K.;Sato, Y.;Osuga, T.;Sato, T.;Iyama, S.;Miyanishi, K.;Takada, K.;Hayashi, T.;Kobune, M.;Kato, J.
转化生长因子-β (TGF-β) 是不同细胞类型上皮-间质转化 (EMT) 的主要诱导剂。 TGF-β介导的EMT被认为有助于肿瘤细胞的扩散和转移。由岩藻糖基转移酶 (FUT) 3 和 FUT6 合成的唾液酸路易斯抗原在转移性结直肠癌 (CRC) 患者中高表达，可用作癌症检测和治疗效果评估的肿瘤标志物。然而，FUT3 和 FUT6 在增强 TGF-β 诱导的 CRC 恶性潜能中的作用尚不清楚。用 FUT3/6 的 siRNA 转染结直肠癌细胞系，并通过细胞增殖、侵袭和迁移测定进行检查。通过western blot分析TGF-β下游分子的表达和磷酸化状态。通过凝集素印迹分析检查 TGF-β 受体 (TβR) 的岩藻糖基化。 siRNA抑制FUT3/6表达，抑制I型TβR的岩藻糖基化和下游分子的磷酸化，从而抑制EMT对CRC细胞的侵袭和迁移。岩藻糖基转移酶 3/6 通过上调唾液酸 Lewis 抗原以及通过 TGF-β 介导的 EMT 增强癌细胞迁移，在癌细胞与内皮细胞的粘附中发挥重要作用。
Transforming growth factor-β (TGF-β) is a major inducer of epithelial–mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear. Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis. Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT. Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.
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影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
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影响因子：
56.9
作者：
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作者：
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DOI：
10.1073/pnas.96.6.3087
发表时间：
1999-03-16
影响因子：
11.1
作者：
Ilyas, M;Efstathiou, JA;Bodmer, WF
通讯作者：
Bodmer, WF
DOI：
10.1073/pnas.1107385108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Liu, Ying-Chih;Yen, Hsin-Yung;Wong, Chi-Huey
通讯作者：
Wong, Chi-Huey