Cancer-associated mutation abolishes the impact of TRIM21 on the invasion of breast cancer cells

Abstract TRIM21 mediates the ubiquitination and proteasomal degradation of Snail, a master regulator of the epithelial to mesenchymal transition, and suppresses the migration and invasion of breast cancer cells. R64Q, a breast cancer-associated TRIM21 mutation, abolishes the interaction between TRIM21 and Snail, and the TRIM21-mediated ubiquitination and degradation of Snail. More importantly, comparing to the xenograft tumors derived from MDA-MB-231 cells with the wild-type TRIM21, xenograft tumors derived from MDA-MB-231 cells with the R64Q mutated TRIM21 showed greatly increased infiltration into neighboring muscle fibers. Furthermore, the R64Q mutation eliminates the effects of TRIM21 on the expression of genes that regulate the epithelial to mesenchymal transition. Collectively, our study demonstrates that the R64Q mutation abolishes the suppressive effects of TRIM21 on the invasion of breast cancer cells.