DIXDC1 Activates the Wnt Signaling Pathway and Promotes Gastric Cancer Cell Invasion and Metastasis
DIXDC1 Activates the Wnt Signaling Pathway and Promotes Gastric Cancer Cell Invasion and Metastasis
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DOI：
10.1002/mc.22290
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发表时间：
2016-04-01
影响因子：
4.6
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Tan, Cong;Qiao, Fan;Wang, Lei
DIXDC 1（Dishevelled-Axin domain containing 1）是一种具有DIX（Dishevelled-Axin）结构域的蛋白，其通过PI 3 K途径促进结肠癌细胞增殖并增加非小细胞肺癌的侵袭和迁移能力。DIXDC 1作为Wnt/β-catenin通路的正调控因子，其在胃癌中的生物学作用以及与Wnt通路的关系尚不清楚。在目前的研究中，DIXDC 1的上调在胃癌中被检测到，并且与晚期TNM分期癌症、淋巴结转移和不良预后相关。我们还发现DIXDC 1的过表达可以促进胃癌细胞的侵袭和迁移。MMPs的上调和E-cadherin的下调参与了这一过程。DIXDC 1增强β-连环蛋白的核积累，从而激活Wnt通路。此外，在DIXDC 1过表达细胞中抑制β-catenin逆转了DIXDC 1的转移促进作用。这些结果表明DIXDC 1的表达与胃癌患者的不良预后相关，DIXDC 1通过激活Wnt通路促进胃癌的侵袭和转移; E-cadherin和MMPs也参与了这一过程。(C)2015 Wiley Periodicals，Inc.
DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E-cadherin were found to be involved in the process. DIXDC1 enhanced -catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of -catenin in DIXDC1-overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E-cadherin and MMPs are also involved in this process. (C) 2015 Wiley Periodicals, Inc.