Dvl2 facilitates the coordination of NF-κB and Wnt signaling to promote colitis-associated colorectal progression.

ABSTRACT: Colitis-associated colorectal cancer (CAC) arises due to prolonged inflammation and has distinct molecular events compared with sporadic colorectal cancer (CRC). Although inflammatory NF-κB signaling was activated by pro-inflammatory cytokines (such as TNFα) in early stages of CAC, Wnt/β-catenin signaling later appears to function as a key regulator of CAC progression. However, the exact mechanism responsible for the cross-regulation between these 2 pathways remains unclear. Here, we found reciprocal inhibition between NF-κB and Wnt/β-catenin signaling in CAC samples, and the Dvl2, an adaptor protein of Wnt/β-catenin signaling, is responsible for NF-κB inhibition. Mechanistically, Dvl2 interacts with the C-terminus of tumor necrosis factor receptor 1 (TNFRI) and mediates TNFRI endocytosis,

SUBMITTER: Tang F 

PROVIDER: S-EPMC8819304 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature