TRIM21 mediates ubiquitination of Snail and modulates epithelial to mesenchymal transition in breast cancer cells

Yue Jin; Yu Zhang; Boyuan Li; Jing Zhang; Zhiwen Dong; Xin Hu; Youzhong Wan

doi:10.1016/j.ijbiomac.2018.11.269

TRIM21 mediates ubiquitination of Snail and modulates epithelial to mesenchymal transition in breast cancer cells

Int J Biol Macromol. 2019 Mar 1:124:846-853. doi: 10.1016/j.ijbiomac.2018.11.269. Epub 2018 Nov 29.

Authors

Yue Jin¹, Yu Zhang¹, Boyuan Li¹, Jing Zhang¹, Zhiwen Dong¹, Xin Hu¹, Youzhong Wan²

Affiliations

¹ National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
² 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. Electronic address: wanyouzhong@jlu.edu.cn.

PMID: 30502437
DOI: 10.1016/j.ijbiomac.2018.11.269

Abstract

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.

Keywords: Epithelial to mesenchymal transition; Snail; TRIM21.

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / metabolism
Adenocarcinoma / mortality
Adenocarcinoma / pathology
Aged
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / mortality
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Data Mining
Databases, Genetic
Epithelial-Mesenchymal Transition / genetics*
Female
Gene Expression Regulation, Neoplastic*
Humans
Kaplan-Meier Estimate
MCF-7 Cells
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Protein Stability
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Ribonucleoproteins / antagonists & inhibitors
Ribonucleoproteins / genetics*
Ribonucleoproteins / metabolism
Signal Transduction
Snail Family Transcription Factors / genetics*
Snail Family Transcription Factors / metabolism
Ubiquitination

Substances

RNA, Small Interfering
Ribonucleoproteins
SNAI1 protein, human
SS-A antigen
Snail Family Transcription Factors