Tripartite Motif Containing 28 (TRIM28) Promotes Breast Cancer Metastasis by Stabilizing TWIST1 Protein

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 15

PMID 27412325

Citations 47

Authors

Chunli Wei

Jingliang Cheng

Boxv Zhou

Li Zhu

Md Asaduzzaman Khan

Tao He

Sufang Zhou

Jian He

Xiaoling Lu

Hanchun Chen

Dianzheng Zhang

Yongxiang Zhao

Junjiang Fu

Affiliations

Soon will be listed here.

Abstract

TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment.

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