TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.

While most Tripartite motif (TRIM) family proteins are E3 ubiquitin ligases, some members have functions beyond the regulation of ubiquitination, impacting normal physiological processes and disease progression. TRIM29, an important member of the TRIM family, exerts a predominant influence on cancer growth, epithelial-to-mesenchymal transition, stemness and metastatic progression by directly potentiating multiple canonical oncogenic pathways. The cancer-promoting effect of TRIM29 is also evident in metabolic interventions and interference with the efficacy of cancer therapeutics. As expected for any key node in cancer, the expression of TRIM29 is tightly regulated by non-coding RNAs, epigenetic modulation, and post-translational regulation. A systematic discussion of how TRIM29 is regulated in cancer, its influences on cancer progression, and its impact on cancer therapeutics is presented in this review. We also explore the context-dependent alterations between TRIM29 function from oncogenic to tumor suppression. As TRIM29 is involved in multiple aspects of cancer progression, a better understanding of its biological impact in cancer may help improve prognosis and develop novel therapeutic combinations, leading to improved personalized cancer care.