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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality.
• AXL, a receptor tyrosine kinase, is implicated in cancer progression and targeted therapy.
• The epithelial-to-mesenchymal transition (EMT) is crucial for cancer metastasis.

Purpose of the Study:

• To investigate the role of AXL in NSCLC.
• To elucidate the molecular mechanisms of AXL's involvement in EMT.
• To explore AXL as a potential therapeutic target in NSCLC.

Main Methods:

• Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
• Western blot analysis to detect protein levels of AXL, EMT markers (Twist, N-cadherin, E-cadherin, β-cadherin).
• RNA interference (RNAi) to downregulate AXL expression.
• MTT and flow cytometry assays to assess cell viability, apoptosis, and cell cycle effects.

Main Results:

• AXL, Twist, and N-cadherin were upregulated, while E-cadherin and β-cadherin were downregulated in PC9 NSCLC cells.
• Downregulation of AXL via RNAi inhibited cell growth and induced apoptosis.
• AXL inhibition attenuated EMT by downregulating Twist and N-cadherin and upregulating E-cadherin and β-cadherin.
• Downregulating Twist did not affect AXL expression levels, suggesting AXL acts upstream of Twist in this pathway.

Conclusions:

• AXL plays a significant role in regulating EMT in NSCLC cells.
• AXL may inhibit EMT by modulating EMT-associated genes.
• AXL's involvement in EMT and cell cycle regulation suggests its clinical significance for NSCLC therapeutic strategies targeting EMT signaling pathways.