These results suggest that PIEZO1 may play a role in promoting a hypoxic and glycolytic tumor environment with increased EMT and angiogenesis driven by TGF-β1, TNF-α via NF-κB, and WNT/β-catenin signaling to promote more aggressive features in high-PIEZO1 HR-negative breast tumors. Here, NFKB1 is linked to breast neoplasm.