Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells

Dong Wang  ¹ , Lixin Bi  ¹ , Jingping Ran  ² , Lei Zhang  ³ , Na Xiao  ³ , Xiaoli Li  ³ Affiliations

• PMID: 34630675
• PMCID: PMC8495543
• DOI: 10.3892/etm.2021.10756

Free PMC article

Abstract

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.

Keywords: apoptosis; growth arrest-specific protein 6/Axl signaling pathway; invasion; migration; proliferation.