The involvement of exosomes in the tumorigenicity of breast cancer cell lines through the crosstalk between STAT3, Notch, and Wnt signaling pathways.

BACKGROUND

Exosomes play a critical role in the tumor microenvironment by interacting with signaling pathways that facilitate breast cancer metastasis, particularly the STAT3 pathway. The STAT3 pathway is essential for tumor progression and aggressiveness, as it interacts with other pathways like Wnt and Notch in particular, triple-negative breast cancer (TNBC) which is the most aggressive form of breast cancer, with a poor prognosis and rapid metastasis. It is exciting to researchers because it is therapeutically challenging and highly invasive. As a result of the lack of specific treatment options, conventional therapy is widely used, which frequently results in relapse.

OBJECTIVES

Elucidate the critical roles of exosomes in modulating breast cancer behaviour and disease progression in TNBC through STAT3 signaling pathways. Specifically, it was focused on the interplay between STAT3 and Wnt or Notch signaling MATERIALS AND METHODS: Exosomes were isolated from one TNBC patient and characterized using electron microscopy and the western blotting technique. This study utilized two subtypes of breast cancer cell lines: non-TNBC and TNBC. AG490 treatment inhibited STAT3 signaling, and then after inhibition, tumorigenic behaviours were evaluated. Gene expression profiles related to the investigated signaling pathways, Wnt and Notch, were detected.

THE RESULTS AND CONCLUSION

Exosomes significantly affect tumor behaviours and chemoresistance and manipulate signaling pathways associated with tumorigenesis, including Wnt/β-catenin and Notch. These results demonstrated the tumorigenic role of exosomes in the TNBC aggressiveness and suggest that their mechanisms may involve Wnt or Notch signaling mediated by the STAT3.