L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer.

L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer.
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L1CAM促进肿瘤进展和转移,是胃癌中独立的不利预后因素。

DOI:
10.1186/1756-8722-6-43
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发表时间:
2013-06-27
影响因子:
28.5
通讯作者:
Xu RH
Xu RH
中科院分区:
医学1区
文献类型:
--
作者:
Chen DL;Zeng ZL;Yang J;Ren C;Wang DS;Wu WJ;Xu RH

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以往的报道表明,L1CAM在多种肿瘤中都有异常表达。L1CAM在胃癌进展和转移中的潜在作用尚不清楚,有待进一步研究。免疫组织化学和Western印迹法检测L1CAM在胃癌组织和细胞系中的表达。分析L1CAM表达与临床病理特征的关系。研究了L1CAM对体外和体内胃癌细胞株增殖、迁移和侵袭的影响。同时观察L1CAM对PI3K/Akt通路的影响。L1CAM在胃癌组织和细胞系中过表达。L1CAM的表达与胃癌患者的侵袭性肿瘤表型和总体生存不良有关。L1CAM在胃细胞系中的异位表达显著促进细胞的增殖、迁移和侵袭,而L1CAM的敲除则在体外抑制细胞的增殖、迁移和侵袭,并在体内抑制肿瘤的发生和转移。异位表达L1CAM后,HGC27细胞中低水平的磷酸化Akt表达上调,而SGC7901细胞中高水平的磷酸化Akt表达被L1CAM下调。此外,LY294002(磷脂酰肌醇-3-激酶抑制剂)或小干扰RNA抑制内源性Akt均可阻断L1CAM过表达促进胃癌细胞的迁移和侵袭。我们的研究表明,L1CAM在胃癌中的过度表达与预后不良有关,在胃癌的进展和转移中起着重要作用。
Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring. Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated. L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA. Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.
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发表时间: 1998-08-03
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发表时间: 2005-02-14
影响因子: 7.8
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