New insights into the ambivalent role and clinical implications of tripartite motif family proteins in colorectal cancer.

Colorectal cancer (CRC) is among the most prevalent malignancies in humans. Despite significant advances over the past few decades, the underlying mechanisms remain incompletely understood. Tripartite motif (TRIM) family proteins have been established as critical players in tumorigenesis, primarily through mediating protein degradation via the ubiquitin-proteasome system (UPS). Accumulating evidence suggests that TRIM family members are involved in CRC progression by regulating multiple cellular processes, exhibiting both tumor-suppressive and oncogenic functions depending on the context. Given the pivotal roles of TRIM proteins in cellular homeostasis and the substantial challenges in CRC treatment, a deeper understanding of their specific contributions to this disease is urgently needed. Therefore, this review systematically outlines the distinct biological functions and molecular mechanisms of various TRIM proteins in CRC, including their roles in tumorigenesis and invasiveness, drug sensitivity, the tumor immune microenvironment (TIME), cell cycle regulation, and metabolic reprogramming. A thorough comprehension of the interactions between TRIM proteins and CRC-related signaling pathways is a crucial prerequisite for exploiting TRIMs as novel biomarkers and potential therapeutic targets in CRC.