National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, China.
Int J Biol Macromol. 2019 Mar 1;124:846-853. doi: 10.1016/j.ijbiomac.2018.11.269. Epub 2018 Nov 29.
Migration and invasion of cancer cells are greatly increased during epithelial to mesenchymal transition (EMT). Depletion of TRIM21 promotes the migration and invasion of MCF7 and T47D cells, and changes the expression of genes that regulate EMT. TRIM21 interacts with Snail, a master regulator of EMT. Overexpression of TRIM21 leads to increased ubiquitination and proteosomal degradation of Snail, while depletion of TRIM21 decreases the ubiquitination of Snail. Importantly, depletion of Snail suppresses the increased migration and invasion of MCF7 and T47D cells promoted by depletion of TRIM21. High-level expression of TRIM21 is associated with longer overall survival in breast cancer. Together, our study demonstrates that TRIM21 modulates EMT by mediating the stability of Snail in breast cancer cells.
癌细胞的迁移和侵袭在上皮间质转化 (EMT) 过程中大大增加。TRIM21 的耗竭促进 MCF7 和 T47D 细胞的迁移和侵袭，并改变调节 EMT 的基因的表达。TRIM21 与 EMT 的主调控因子 Snail 相互作用。TRIM21 的过表达导致 Snail 的泛素化和蛋白酶体降解增加，而 TRIM21 的耗竭减少了 Snail 的泛素化。重要的是，Snail 的耗竭抑制了由 TRIM21 耗竭促进的 MCF7 和 T47D 细胞迁移和侵袭的增加。TRIM21 的高表达与乳腺癌患者的总生存时间延长有关。综上所述，我们的研究表明，TRIM21 通过调节乳腺癌细胞中 Snail 的稳定性来调节 EMT。
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