IER5L promotes p53 degradation via TRAF7-mediated ubiquitination to facilitate EMT and colorectal cancer malignancy.

Colorectal cancer is a leading cause of cancer-related death worldwide. The role of immediate early response 5-like (IER5L) in colorectal cancer remains unknown. This study investigated IER5L expression, biological function, and molecular mechanism in colorectal cancer. IER5L was significantly overexpressed in tumor tissues and cell lines. High IER5L expression correlated with poor patient prognosis. Functional assays demonstrated that IER5L promoted proliferation, migration, invasion, epithelial-mesenchymal transition, and liver metastasis in vitro and in vivo. Mechanistically, IER5L bound directly to the E3 ubiquitin ligase TRAF7. This interaction facilitated K48-linked ubiquitination and proteasomal degradation of the tumor suppressor p53. Restoring p53 expression reversed IER5L-driven malignant phenotypes. TRAF7 knockdown or mutation of its lysine 451 residue, a critical IER5L binding site, abrogated IER5L effects. The IER5L-TRAF7-p53 axis represents a previously unrecognized driver of colorectal cancer progression. These findings provide mechanistic insight and suggest potential therapeutic targets for colorectal cancer.