AXL is associated with STAT3 activation in breast cancer.

Breast cancer (BC) represents one of the most frequently occurring malignancies and a primary cause of cancer-associated mortality among women globally. AXL, a receptor tyrosine kinase of the TAM family, and signal transducer and activator of transcription 3 (STAT3) are both aberrantly activated in BC and contribute to tumor progression. The present study aimed to investigate the functional association between AXL and STAT3 activation in BC. It was found that the overexpression of AXL in MCF7 and 293T cells enhanced STAT3 phosphorylation and transcriptional activity, whereas AXL knockdown using short hairpin RNA or pharmacological inhibition with R428 suppressed STAT3 activation. AXL overexpression also enhanced the secretion of IL-6, a major upstream activator of STAT3. Bioinformatics analysis of clinical BC datasets (GSE102484, GSE9893 and The Cancer Proteome Atlas) validated a positive correlation between AXL expression and STAT3 signaling activation. Collectively, these findings demonstrate that AXL is associated with STAT3 activation in BC, providing insight into the molecular pathways driving BC progression and uncovering candidate therapeutic targets.