TRIM21-mediated OGT degradation inhibits breast cancer tumorigenesis and metastasis

A variety of studies have indicated that the E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) plays a crucial role in the development and progression of various tumors. However, the specific functional mechanisms of TRIM21 in breast cancer, particularly in triple-negative breast cancer (TNBC), remain unclear. This study revealed that TRIM21 expression is reduced in breast cancer tissues and decreased in TNBC patients. We revealed that low TRIM21 expression is closely associated with certain clinicopathological features and shorter survival in breast cancer patients. Our results demonstrate that TRIM21 can inhibit the proliferation and migration of breast cancer cells both in vivo and in vitro. Mechanistically, we discovered that TRIM21 can directly bind to O-GlcNAc transferase (OGT) and mediate its K48-linked ubiquitination and degradation. Our rescue experiments confirmed that OGT plays a key role in the TRIM21-mediated suppression of breast cancer progression. Furthermore, our detection and analysis of breast cancer patient tissue samples further validated the critical role of OGT in TRIM21-regulated breast cancer, particularly in TNBC patients. In summary, our study illustrates that TRIM21 is not only a biomarker with significant predictive value but also a potential therapeutic target for breast cancer patients.