AXL is associated with STAT3 activation in breast cancer

  • Mol Clin Oncol. 2026 Aug 6;25(4):60. doi: 10.3892/mco.2026.2969.
Guoan Zhang  1  2 ,  Xiaobai Sun  3 ,  Junping Zhang  4 ,  Zhaozhen Zhang  1  2 ,  Xinlin Luan  1  2 ,  Fengyuan Yu  1  2 ,  Zhenjie Guan  1  2 ,  Changming Guo  1  2 ,  Yangyang Hu  1  2 ,  Mengfei Zhao  1  2 ,  Jiarong E  1  2 ,  Yingxin Xiong  1  2 ,  Junze Liu  1  2 ,  Yuqing Hu  5 ,  Xinyu Ma  5 ,  Ruiyao Yang  5 ,  Jianli Liu  6 ,  Hongli Zhao  7 ,  Qingwei Guo  8
Affiliations
  • 1. School of Forensic Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China.
  • 2. Jining Key Laboratory of Forensic Multimodal Precision Identification, Jining, Shandong 272067, P.R. China.
  • 3. Department of Medical Technology, Jinan Vocational College of Nursing, Jinan, Shandong 250102, P.R. China.
  • 4. Department of Pathology, Liangshan People's Hospital, Jining, Shandong 272600, P.R. China.
  • 5. School of Mental Health (Research Institute of Mental Health), Jining Medical University, Jining, Shandong 272067, P.R. China.
  • 6. Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
  • 7. Department of Gastroenterology, Digestive Diseases Hospital of Shandong First Medical University, Jining, Shandong 272067, P.R. China.
  • 8. Department of Hematology and Oncology, and Department of Child Health, Jinan Children's Hospital, Jinan, Shandong 250022, P.R. China.
PMID: 42614716 DOI: 10.3892/mco.2026.2969
Abstract

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.

Keywords
AXL; breast cancer; signal transducer and activator of transcription 3.
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