This study investigates the role of NF-κB in intestinal tumorigenesis, focusing on the bidirectional conversion between tumor-initiating stem cells and non-stem cells. Using a genetic model of intestinal epithelial cell (IEC)-restricted constitutive Wnt-activation, the authors demonstrate that NF-κB modulates Wnt signaling. Specifically, IEC-specific ablation of Rela/p65 retards crypt stem cell expansion, while elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of non-stem cells, which acquire tumor-initiating capacity. The findings support the concept of a bidirectional conversion and highlight the importance of inflammatory signaling in dedifferentiation and the generation of tumor-initiating cells in vivo. The study also explores the interaction between NF-κB and β-catenin, showing that NF-κB can enhance β-catenin signaling through recruitment of CBP. Additionally, the authors demonstrate that villus cells can dedifferentiate and form spheroids with tumor-forming capacity, suggesting that dedifferentiation of non-stem cells can lead to tumor initiation. The results provide genetic evidence for the existence of dedifferentiation in intestinal tumorigenesis and suggest that both "top-down" and "bottom-up" models of adenoma morphogenesis may coexist.This study investigates the role of NF-κB in intestinal tumorigenesis, focusing on the bidirectional conversion between tumor-initiating stem cells and non-stem cells. Using a genetic model of intestinal epithelial cell (IEC)-restricted constitutive Wnt-activation, the authors demonstrate that NF-κB modulates Wnt signaling. Specifically, IEC-specific ablation of Rela/p65 retards crypt stem cell expansion, while elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of non-stem cells, which acquire tumor-initiating capacity. The findings support the concept of a bidirectional conversion and highlight the importance of inflammatory signaling in dedifferentiation and the generation of tumor-initiating cells in vivo. The study also explores the interaction between NF-κB and β-catenin, showing that NF-κB can enhance β-catenin signaling through recruitment of CBP. Additionally, the authors demonstrate that villus cells can dedifferentiate and form spheroids with tumor-forming capacity, suggesting that dedifferentiation of non-stem cells can lead to tumor initiation. The results provide genetic evidence for the existence of dedifferentiation in intestinal tumorigenesis and suggest that both "top-down" and "bottom-up" models of adenoma morphogenesis may coexist.