Trim21 is an E3 ligase that is involved in the regulation of metastasis. High-level expression of TRIM21 is associated with good prognosis of breast cancer. After transplantation in immunodeficient mice, TRIM21-depleted MCF7 cells form tumors that show evident local invasion, i.e., extensive infiltration of single tumor cells into nearby muscle fibers. Knockdown of TRIM21 increases the migration and invasion of MCF7 and T47D cells by altering the expression of genes that regulate epithelial to mesenchymal transition(EMT). TRIM21 interacts with Snail, a master regulator of EMT, and the B-Box domain of TRIM21 is essential for the interaction between TRIM21 and Snail. Overexpression of TRIM21 leads to increased ubiquitination and subsequent proteosomal degradation of Snail, while depletion of TRIM21 decreases the ubiquitination and degradation of Snail. Most Importantly, knockdown of Snail suppresses the increased migration and invasion of MCF7 and T47D cells caused by TRIM21 knockdown. Collectively, our study demonstrates that TRIM21 modulates EMT by mediating the stability of Snail in breast cancer cells.
Citation Format: Xin Hu, Yue Jin, Yu Zhang, Boyuan Li, Youzhong Wan. TRIM21 suppresses invasion of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 161.