Extracellular adenosine triphosphate upregulates S100A4 expression and promotes the migration and invasion of breast cancer cells via P2Y2/SOX9 signaling

Background

The tumor microenvironment (TME), composed of tumor cells, mesenchymal cells, and diverse extracellular molecules, plays a pivotal regulatory role in tumor initiation, malignant progression, and the development of anti-cancer therapeutic resistance. Extracellular adenosine triphosphate (ATP) is a critical bioactive signaling molecule in the TME. Previous studies from our group have confirmed that extracellular ATP is extensively involved in multiple malignant phenotypes of prostate cancer and breast cancer, including tumor cell migration, invasion, chemotherapeutic resistance, and the maintenance of cancer stem cell properties. In our prior work, we demonstrated that extracellular ATP acts on stromal fibroblasts in the breast cancer microenvironment to facilitate the formation of a pro-tumorigenic niche. However, the full molecular mechanism governing this regulatory axis remains incompletely elucidated. Here, we aim to uncover its underlying mechanism, thereby providing new insights for the development of breast cancer therapeutic strategies.