Role of ES Cell-Expressed Ras (ERas) in Tumorigenicity of Gastric Cancer
Role of ES Cell-Expressed Ras (ERas) in Tumorigenicity of Gastric Cancer
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DOI：
10.2353/ajpath.2010.091056
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发表时间：
2010-08-01
影响因子：
6
通讯作者：
Joh, Takashi
中科院分区：
文献类型：
--
作者：
Kubota, Eiji;Kataoka, Hiromi;Joh, Takashi
ERas是Ras家族的一个独特成员，最初仅在胚胎干细胞（ES）中发现，它在移植的ES细胞转化为畸胎瘤中起着至关重要的作用。ERas参与ES细胞存活，并且与其他Ras家族成员不同，其组成型活性没有任何突变。本研究的目的是探讨ER α在胃癌中的表达及其作用。为了测试ER as是否在人类癌细胞中发挥重要作用，我们检测了其在胃癌中的表达和功能。ER α在胃癌细胞系中有不同程度的表达。ERas表达的诱导激活磷脂酰肌醇3激酶（PI 3 K）/Akt轴，然后增强锚定非依赖性生长，并且通过siRNA敲低ERas抑制细胞侵袭。免疫组化结果显示，38.7%（55/142）的胃癌组织表达ERas，其表达与胃癌的肝转移（P < 0.0001）和淋巴结转移（P < 0.05）有关。ERas上调转录调节因子包括ZFHX 1A、ZFHX 1B和TCF 3，它们抑制E-cadherin。这些数据表明，ERas在胃癌的显著群体中被激活，其中它可能通过下调E-钙粘蛋白在胃癌细胞存活和向肝转移中起关键作用。(Am J Pathol 2010，177：955-963; DOI：10.2353/ajpath.2010.091056）
ERas, a unique member of the Ras family, was initially found only in embryonic stem (ES) cells, where it plays a crucial role in the transformation of transplanted ES cells to teratomas. ERas is involved in ES cell survival, and unlike other Ras family members, is constitutively active without any mutations. The aim of this study was to investigate the expression and role of ERas in human gastric cancer. To test whether ERas played a significant role in human cancer cells, we examined its expression and function in gastric cancer. ERas was expressed in gastric cancer cell lines at different levels. Induction of ERas expression activated the phosphatidylinositol 3 kinase (PI3K)/Akt axis and then enhanced anchorage-independent growth and ERas knockdown by siRNA suppressed cell invasion. Immunohistochemical analyses revealed that ERas was expressed in 38.7% (55/142) of human gastric carcinoma tissues, and its expression was significantly associated with metastasis to the liver (P < 0.0001) and lymph nodes (P < 0.05). ERas up-regulated transcription regulatory factors including ZFHX1A, ZFHX1B, and TCF3, which repress E-cadherin. These data suggest that ERas is activated in a significant population of gastric cancer, where it may play a crucial role in gastric cancer cell survival and metastases to liver via down-regulation of E-cadherin. (Am J Pathol 2010, 177:955-963; DOI: 10.2353/ajpath.2010.091056)