Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells
Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells
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DOI：
10.3892/etm.2021.10756
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发表时间：
2021-11-01
影响因子：
2.7
通讯作者：
Li, Xiaoli
中科院分区：
文献类型：
--
作者：
Wang, Dong;Bi, Lixin;Li, Xiaoli
多项研究表明，生长抑制特异性蛋白6 （growth arrest-specific protein 6, Gas6）和Axl在肾细胞和食管癌等多种肿瘤组织中高表达。然而，Gas6/Axl信号通路在肺腺癌中的作用尚不清楚。本研究旨在探讨Gas6/Axl信号通路对肺腺癌细胞的影响及其作用机制，为肺腺癌的临床治疗提供新的靶点。利用人肺腺癌组织检测Gas6/Axl信号通路的激活情况。并以人肺腺癌细胞系A549为实验对象，研究Gas6/Axl信号通路对肺腺癌细胞增殖、迁移、侵袭和凋亡的影响。利用重组人Gas6蛋白和抑制剂TP-0903分别激活和抑制Gas6/Axl信号通路。结果显示，人肺腺癌组织中Gas6和Axl的表达水平明显高于邻近健康组织。TP-0903抑制Gas6/Axl信号通路后，p21、p53、caspase 3、caspase 8、caspase 9在A549细胞中表达水平升高。当Gas6/Axl信号通路被激活时，观察到相反的效果。此外，通过创面愈合和Transwell侵袭试验测定A549细胞的迁移和侵袭能力。结果表明，激活Gas6/Axl信号通路后，A549细胞的迁移和侵袭能力显著增强，而抑制Gas6/Axl信号通路则相反。细胞计数试剂盒8和克隆形成实验表明，Gas6/Axl信号通路的活性与细胞增殖呈正相关。综上所述，Gas6/Axl信号通路促进肺腺癌细胞的增殖、迁移和侵袭，抑制肺腺癌细胞的凋亡，在肺腺癌的发展过程中起重要作用。
Several studies have demonstrated that growth arrest-specific protein 6 (Gas6) and Axl are highly expressed in various tumor tissues, such as renal cell and esophageal carcinoma. However, the effect of the Gas6/Axl signaling pathway on lung adenocarcinoma is still unclear. The aim of the present study was to investigate the effect of the Gas6/Axl signaling pathway on lung adenocarcinoma cells and its mechanism of action, which may provide a novel target for the clinical treatment of lung adenocarcinoma. Human lung adenocarcinoma tissues were used to examine the activation of the Gas6/Axl signaling pathway. In addition, the human lung adenocarcinoma cell line A549 was employed to study the effects of the Gas6/Axl signaling pathway on the proliferation, migration, invasion and apoptosis of lung adenocarcinoma cells. Recombinant human Gas6 protein and inhibitor TP-0903 were used to activate and inhibit the Gas6/Axl signaling pathway, respectively. The results revealed that Gas6 and Axl expression level was increased in human lung adenocarcinoma tissues compared with adjacent healthy tissues. After inhibition of the Gas6/Axl signaling pathway with TP-0903, p21, p53, caspase 3, caspase 8 and caspase 9 exhibited higher expression level in A549 cells. The opposite effect was observed when the Gas6/Axl signaling pathway was activated. In addition, the migratory and invasive ability of A549 cells was determined via wound-healing and Transwell invasion assays. The results indicated that the migratory and invasive ability of A549 cells was significantly increased when the Gas6/Axl signaling pathway was activated and inhibition of Gas6/Axl signaling pathway caused the opposite results. Activity of Gas6/Axl signaling pathway was shown to be positively associated with cell proliferation by Cell Counting Kit 8 and clone formation assays. In conclusion, the Gas6/Axl signaling pathway was revealed to promote the proliferation, migration and invasion and inhibit the apoptosis of lung adenocarcinoma cells, which serve important roles in the progression of lung adenocarcinoma.