State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong Feng East Load, Guangzhou 510060, China.
J Hematol Oncol. 2013 Jun 27;6:43. doi: 10.1186/1756-8722-6-43.
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.
先前的报告表明，L1cam 在各种肿瘤中异常表达。L1cam 在胃癌进展和转移中的潜在作用尚不清楚，需要进一步研究。
通过免疫组织化学和 Western blot 检测胃癌组织和细胞系中 L1cam 的表达。分析 L1cam 表达与临床病理特征的关系。在体外和体内研究 L1cam 在胃癌细胞系中的增殖、迁移和侵袭作用。还评估了 L1cam 对 PI3K/Akt 通路的影响。
L1cam 在胃癌组织和细胞系中过度表达。L1cam 的表达与胃癌患者侵袭性肿瘤表型和总体生存率降低相关。在胃细胞系中异位表达 L1cam 显著促进细胞增殖、迁移和侵袭，而敲低 L1cam 则抑制细胞增殖、迁移和侵袭以及体内肿瘤发生和转移。HGC27 细胞中磷酸化 Akt 的低水平在 L1cam 异位表达后上调，而 SGC7901 细胞中磷酸化 Akt 的高水平在 L1cam 敲低后受到抑制。此外，L1cam 过表达在胃癌细胞中促进的迁移和侵袭可以通过应用 LY294002（一种磷酸肌醇-3-激酶抑制剂）或通过小干扰 RNA 敲低内源性 Akt 来消除。
我们的研究表明，在胃癌中过度表达且与预后不良相关的 L1cam 在胃癌的进展和转移中发挥重要作用。
