As a possible mechanism, our results demonstrate that increased PIEZO1 expression levels are correlated with the upregulation of gene sets associated with cancer aggressiveness, including EMT, hypoxia, apical junction, angiogenesis, and glycolysis with multiple signaling pathways, including TGF-β1, TNF-α via NF-κB, and WNT/β-catenin, in high-PIEZO1 HR-negative tumors. The gene discussed is NFKB1; the disease is cancer.