Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway
Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway
复制标题
蛋白 O-岩藻糖基转移酶 1 的过度表达通过 Notch 信号通路加速肝细胞癌的进展。
DOI：
10.1016/j.bbrc.2016.03.062
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发表时间：
2016-04-29
影响因子：
3.1
通讯作者：
Wang, Xiaoying
中科院分区：
文献类型：
--
作者：
Ma, Like;Dong, Pingping;Wang, Xiaoying
Notch 信号的异常激活经常发生在肝癌中，并且与肝脏恶性肿瘤相关。然而，调节肝细胞癌（HCC）病理性Notch激活的机制仍不清楚。蛋白 O-岩藻糖基转移酶 1 (Pofut1) 催化 O-连接岩藻糖添加到 Notch 的表皮生长因子样重复序列中。在本研究中，我们检测了Pofut1在8个HCC细胞系和253个人HCC组织中的表达。我们报道Pofut1在HCC细胞系和临床HCC组织中过表达，并且Pofut1过表达在临床上与HCC的不利生存和高疾病复发相关。体外实验表明Pofut1过表达加速了HCC细胞的增殖和迁移。此外，Pofut1过表达促进Notch配体Dll1与Notch受体的结合，从而激活HCC细胞中的Notch信号通路，表明Pofut1过表达可能是HCC中Notch信号异常激活的原因。综上所述，我们的研究结果表明，异常激活的 Pofut1-Notch 通路与 HCC 进展有关，阻断该通路可能是 HCC 治疗的一种有前景的策略。 (C) 2016 Elsevier Inc. 保留所有权利。
Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofutl overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. (C) 2016 Elsevier Inc. All rights reserved.