Ran GTPase Induces EMT and Enhances Invasion in Non-Small Cell Lung Cancer Cells Through Activation of PI3K-AKT Pathway
Ran GTPase Induces EMT and Enhances Invasion in Non-Small Cell Lung Cancer Cells Through Activation of PI3K-AKT Pathway
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DOI：
10.3727/096504013x13747716581417
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发表时间：
2013-01-01
影响因子：
3.1
通讯作者：
Xu, Shidong
中科院分区：
文献类型：
--
作者：
Ning, Jinfeng;Liu, Wei;Xu, Shidong
Ras 相关核蛋白 (Ran) GTPase 在非小细胞肺癌 (NSCLC) 细胞中表达上调，并且是 NSCLC 细胞存活所必需的。然而，Ran 对 NSCLC 细胞侵袭和上皮间质转化 (EMT) 的影响仍不清楚。这项研究发现，Ran 表达在高侵袭性 NSCLC 细胞中比在低侵袭性 NSCLC 细胞中高得多。 Ran 的异位表达增强了 NSCLC 细胞的侵袭并诱导 EMT。 LY294002 对 PI3K-AKT 通路的抑制，而非 PD98509 对 MEK-ERK 通路的抑制，逆转了 Ran 过表达诱导的这些细胞中的上述效应。总之，我们的研究结果表明 Ran 通过激活 PI3K-AKT 信号传导诱导 EMT 并增强 NSCLC 细胞的侵袭。因此，Ran可能是NSCLC治疗干预的潜在靶点。
Ras-related nuclear protein (Ran) GTPase is upregulated in non-small cell lung cancer (NSCLC) cells and is required for NSCLC cell survival. However, the effect of Ran on NSCLC cell invasion and epithelial to mesenchymal transition (EMT) remains unclear. This study found that Ran expression was much higher in highly invasive NSCLC cells than in lowly invasive NSCLC cells. Ectopic expression of Ran enhanced invasion and induced EMT in NSCLC cells. Inhibition of the PI3K-AKT pathway by LY294002, but not the MEK-ERK pathway by PD98509, reversed the above effects in these cells induced by Ran overexpression. In conclusion, our findings demonstrate that Ran induces EMT and enhances invasion in NSCLC cells through the activation of PI3K-AKT signaling. Thus, Ran may be a potential target for NSCLC therapeutic intervention.