Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion
Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion
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DOI：
10.1158/0008-5472.can-06-2359
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发表时间：
2006-11-01
期刊：
影响因子：
11.2
通讯作者：
Kikuchi, Akira
中科院分区：
文献类型：
--
作者：
Kurayoshi, Manabu;Oue, Naohide;Kikuchi, Akira
Wnt-5a是激活Writ信号传导中的β-连环蛋白依赖性途径的代表性配体。尽管在人类癌症中经常观察到β-连环蛋白依赖性通路的异常激活，但β-连环蛋白非依赖性通路与肿瘤发生的关系尚不清楚。我们试图阐明Wnt-5a如何参与胃癌的侵袭性。应用免疫组化方法检测了237例胃癌组织中71例Wnt-5a的异常表达。Wnt-5a阳性表达与胃癌的临床分期及预后有关。Wnt-5a具有促进胃癌细胞迁移和侵袭的能力。Wnt-5a激活粘着斑激酶和小GTP结合蛋白Rac，已知这两者在细胞迁移中起作用。在Wnt-5a敲低的细胞中，细胞迁移、膜皱褶和桩蛋白的周转受到抑制。此外，抗Wnt-5a抗体抑制胃癌细胞迁移。这些结果表明，Wnt-5a通过调节粘着斑复合物刺激细胞迁移，Wnt-5a不仅是胃癌的预后因子，而且是一个很好的治疗靶点。
Wnt-5a is a representative ligand that activates a beta-cateninin-dependent pathway in the Writ signaling. Although abnormal activation of beta-catenin-dependent pathway is often observed in human cancer, the relationship between beta-catenin-independent pathway and tumorigenesis is not clear. We sought to clarify how Wnt-5a is involved in aggressiveness of gastric cancer. Abnormal expression of Wnt-5a was observed in 71 of 237 gastric cancer cases by means of immunohistochemistry. The positivity of Wnt-5a expression was correlated with advanced stages and poor prognosis of gastric cancer. Wnt-5a had the abilities to stimulate cell migration and invasion in gastric cancer cells. Wnt-5a activated focal adhesion kinase and small GTP-binding protein Rac, both of which are known to play a role in cell migration. Cell migration, membrane ruffling, and turnover of paxillin were suppressed in Wnt-5a knockdown cells. Furthermore, anti-Wnt-5a antibody suppressed gastric cancer cell migration. These results suggest that Wnt-5a stimulates cell migration by regulating focal adhesion complexes and that Wnt-5a is not only a prognostic factor but also a good therapeutic target for gastric cancer.