Mechanistic studies demonstrated that Nrf2-mediated PSMD4 expression may promote more than just colony formation, cell invasion, and soft agar growth, and may also confer 5-FU resistance in colon cancer cells via the NF-κB/AKT/β-catenin/ZEB1 cascade. The gene discussed is NFKB1; the disease is malignant colon neoplasm.