Zhu Liangming, Wang Zhou, Lin Yuxia, Chen Zhitao, Liu Haibo, Chen Ying, Wang Ningning, Song Xiue
Department of Thoracic Surgery, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China.
Department of Thoracic Surgery, Shandong Province Hospital, Shandong University, Jinan, Shandong 250013, P.R. China.
Oncol Rep. 2015 Mar;33(3):1257-63. doi: 10.3892/or.2014.3683. Epub 2014 Dec 19.
Sphingosine kinase 1 (SphK1) has been shown to play an important role in the progression of a number of human cancers. It has been reported that the expression of SphK1 is greatly elevated in non-small cell lung cancer (NSCLC) tissues. However, its role and underlying mechanisms in NSCLC have not been fully elucidated. In the present study, we found that SphK1 was highly expressed in NSCLC cells. Overexpression of SphK1 promoted the invasion and migration of NSCLC cells, while knockdown of SphK1 suppressed the invasion and migration. Furthermore, we demonstrated that SphK1 decreased the protein level of E-cadherin, yet increased the protein level of Snail. In addition, SphK1 was able to stimulate the activation of AKT. Inhibition of the AKT pathway attenuated the biological functions of NSCLC cells induced by overexpression of SphK1. Taken together, our findings suggest that SphK1 can enhance the invasion and migration of NSCLC cells via activation of the AKT pathway and regulation of E-cadherin and Snail expression. Thus, SphK1 could be a potential target for the detection and treatment of NSCLC.
鞘氨醇激酶1（SphK1）已被证明在多种人类癌症的进展中起重要作用。据报道，SphK1在非小细胞肺癌（NSCLC）组织中的表达显著升高。然而，其在NSCLC中的作用及潜在机制尚未完全阐明。在本研究中，我们发现SphK1在NSCLC细胞中高表达。SphK1的过表达促进了NSCLC细胞的侵袭和迁移，而敲低SphK1则抑制了侵袭和迁移。此外，我们证明SphK1降低了E-钙黏蛋白的蛋白水平，但增加了Snail的蛋白水平。另外，SphK1能够刺激AKT的激活。抑制AKT途径减弱了SphK1过表达诱导的NSCLC细胞的生物学功能。综上所述，我们的研究结果表明，SphK1可通过激活AKT途径以及调节E-钙黏蛋白和Snail的表达来增强NSCLC细胞的侵袭和迁移。因此，SphK1可能是NSCLC检测和治疗的潜在靶点。
