Taken together, our results demonstrated that STIM2 specifically regulates NFAT1, which in turn regulates the expression and secretion of TGF-β1 to promote EMT in vitro and in vivo, leading to metastasis of breast cancer.
This study showed that FOXP1 has protein-protein interaction with NFAT1 on DNA and enhances breast cancer cell migration by repressing NFAT1 transcriptional activity and FOXP1 shows oncogenic function by regulating breast cancer cell motility.
We also propose several strategies for inhibiting the NFAT1-MDM2-p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy.
These data point to a mechanism by which NFAT1 orchestrates the communication between breast cancer cells and host neutrophils during breast cancer progression.
Importantly, analysis of a matched breast cancer progression tissue microarray revealed a negative correlation between levels of NFAT1 and Stat5 (pY694) during the progression of breast cancer.