Our results suggest for the first time that ESM-1 is the most overexpressed gene in RT-R-MDA-MB-231 cells compared to MDA-MB-231 cells and plays a critical role in tumorigenesis in breast cancer (Figure 7) through regulation of PDK, PKC, and ERK1/2 pathways and the subsequent activation of transcription factors HIF-1α, NF-κB, and STAT-3 to regulate adhesion molecules, MMPs, and VEGF. Here, STAT3 is linked to breast cancer.