Cancer-associated mutation abolishes the impact of TRIM21 on the invasion of breast cancer cells
Cancer-associated mutation abolishes the impact of TRIM21 on the invasion of breast cancer cells
复制标题
癌症相关突变消除了 TRIM21 对乳腺癌细胞侵袭的影响。
DOI：
10.1016/j.ijbiomac.2019.10.019
复制
发表时间：
2020-01-01
影响因子：
8.2
通讯作者：
Wan, Youzhong
中科院分区：
文献类型：
--
作者：
Jin, Yue;Zhao, Xinyue;Wan, Youzhong
TRIM21介导Snail的泛素化和蛋白酶体降解，Snail是上皮向间充质转化的主要调节因子，并抑制乳腺癌细胞的迁移和侵袭。R64Q是一个乳腺癌相关的TRIM21突变，它取消了TRIM21与Snail的相互作用，以及TRIM21介导的Snail的泛素化和降解。更重要的是，与野生型TRIM21的MDA-MB-231细胞来源的移植瘤相比，R64Q突变的TRIM21突变的MDA-MB-231细胞来源的移植瘤对邻近肌肉纤维的侵袭显著增加。此外，R64Q突变消除了TRIM21对调节上皮向间充质转化的基因表达的影响。总之，我们的研究表明，R64Q突变取消了TRIM21对乳腺癌细胞侵袭的抑制作用。(C)2019爱思唯尔B.V.保留所有权利。
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. (C) 2019 Elsevier B.V. All rights reserved.