AXL Transcriptionally Up-regulates ISG15 Expression to Mediate Cell Proliferation in Non-small-cell Lung Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• The AXL receptor tyrosine kinase (AXL) drives tumor progression and chemoresistance in non-small-cell lung cancer (NSCLC).
• The precise molecular mechanisms of AXL-driven oncogenesis in NSCLC are not fully understood.

Purpose of the Study:

• To identify novel downstream genes regulated by AXL in NSCLC.
• To elucidate the role of these genes in NSCLC progression and chemoresistance.

Main Methods:

• Transcriptomic RNA sequencing was employed to identify AXL-regulated genes.
• Cellular proliferation was assessed using CCK-8 assays, and glucose uptake was measured.
• Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and promoter activity assays were used to analyze interferon-stimulated gene 15 (ISG15) expression and regulation by AXL.

Main Results:

• RNA sequencing identified ISG15 as a novel downstream target of AXL.
• ISG15 expression significantly increased cellular proliferation and glucose uptake in NSCLC cells.
• AXL was found to transcriptionally upregulate ISG15 by modulating its 5'-promoter activity.

Conclusions:

• ISG15 is a newly identified downstream target of AXL in NSCLC.
• ISG15 plays a role in promoting NSCLC cell proliferation and glucose metabolism.
• ISG15 represents a potential therapeutic target for overcoming AXL-mediated resistance in NSCLC.