Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer

Abstract

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. AXL, which is a member of the receptor tyrosine kinases, has been established as a strong candidate for the targeted therapy of cancer. Therefore, the present study aimed to investigate the role of AXL in NSCLC; in particular the molecular mechanisms underlying the involvement of AXL in the epithelial-to-mesenchymal transition (EMT). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis demonstrated that AXL, EMT-inducing Twist and the mesenchymal marker N-cadherin were upregulated, and the epithelial markers E-cadherin and β-cadherin were downregulated, in the PC9 NSCLC cell line. Furthermore, downregulation of AXL expression by RNA interference was shown to inhibit cell growth by inducing the apoptosis of PC9 cells, as demonstrated by MTT and flow cytometry analyses. Notably, inhibition of AXL attenuated the regulation of EMT-associated genes, specifically downregulating Twist and N-cadherin, and upregulating E-cadherin and β-cadherin. Conversely, downregulation of Twist did not affect the expression levels of AXL. These results suggested that AXL may inhibit the EMT by the regulation of EMT-associated genes in the PC9 cell line. The results of the present study indicated that AXL may have a role in the regulation of EMT and the cell cycle of the PC9 cells; thus suggesting that AXL may have clinical significance in the design of therapeutic strategies targeting NSCLC and EMT signaling pathways.