SHIP1 inhibits cell growth, migration, and invasion in non-small cell lung cancer through the PI3K/AKT pathway
SHIP1 inhibits cell growth, migration, and invasion in non-small cell lung cancer through the PI3K/AKT pathway
复制标题
SHIP1通过PI3K/AKT通路抑制非小细胞肺癌细胞生长、迁移和侵袭
DOI：
10.3892/or.2019.6990
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发表时间：
2019-04-01
期刊：
影响因子：
4.2
通讯作者：
Song, Xin
中科院分区：
文献类型：
--
作者：
Fu, Qiaofen;Huang, Yuhui;Song, Xin
SRC同源2-含肌醇-5‘-磷酸酶1(SHIP1)在血液系统肿瘤的发生和发展中起重要作用，但对SHIP1在包括肺癌在内的各种实体肿瘤中的作用知之甚少。本研究旨在探讨SHIP1在非小细胞肺癌中的表达及其作用机制。基因表达数据库显示SHIP1在非小细胞肺癌中低表达。使用新鲜组织和细胞系的进一步研究也证实了这一观察结果。生物学功能分析表明，SHIP1过表达显著抑制了NSCLC细胞的生长、迁移和侵袭。机制分析表明，SHIP1失活了PI3K/AKT信号通路，抑制了与细胞周期和上皮-间充质转化相关的信号。在临床标本中，SHIP1降低是一个不利因素，且与T分期、N分期和临床分期呈负相关。此外，与SHIP1蛋白水平高的患者相比，SHIP1水平低的患者存活率降低。值得注意的是，SHIP1基因的启动子缺乏CpG岛，SHIP1表达的抑制与表皮生长因子受体或Kirsten鼠肉瘤突变无关。因此，本研究证实SHIP1通过PI3K/AKT途径抑制非小细胞肺癌细胞的生长、迁移和侵袭。此外，SHIP1表达降低可能是NSCLC的不利因素。
Src homology 2-containing inositol-5 '-phosphatase 1 (SHIP1) serves a vital role in the occurrence and development of hematological tumors, but there is limited knowledge regarding the role of SHIP1 in various solid tumors, including lung cancer. In the present study, the aim was to investigate the expression and functional mechanisms of SHIP1 in non-small cell lung cancer (NSCLC). The Gene Expression Omnibus database demonstrated that SHIP1 had low expression in NSCLC. Further studies using fresh tissues and cell lines also confirmed this observation. Biological function analyses revealed that SHIP1 overexpression notably suppressed cell growth, migration and invasion in vitro and in vivo in NSCLC. Mechanistic analyses indicated that SHIP1 inactivated the phosphoinositide 3-kinase (PI3K)/AKT pathway to suppress signals associated with the cell cycle and epithelial-mesenchymal transition. In clinical specimens, reduced SHIP1 is an unfavorable factor and is negatively associated with the T classification, N classification and clinical stage. Furthermore, patients with low SHIP1 levels exhibited reduced survival rate, compared with patients with high levels of the protein. Notably, the promoter of the SHIP1 gene lacks CpG islands, and the suppression of SHIP1 expression is not associated with epidermal growth factor receptor or Kirsten rat sarcoma mutations. Thus, the present study demonstrated that SHIP1 inhibits cell growth, migration and invasion in NSCLC through the PI3K/AKT pathway. Additionally, reduced SHIP1 expression may be an unfavorable factor for NSCLC.