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Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer

Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the p...

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Autores principales: Ye, Runyi, AiErken, NiJiati, Kuang, Xiaying, Zeng, Huijuan, Shao, Nan, Lin, Ying, Liu, Pian, Wang, Shenming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433133/
https://www.ncbi.nlm.nih.gov/pubmed/34508066
http://dx.doi.org/10.1038/s41389-021-00350-x
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author Ye, Runyi
AiErken, NiJiati
Kuang, Xiaying
Zeng, Huijuan
Shao, Nan
Lin, Ying
Liu, Pian
Wang, Shenming
author_facet Ye, Runyi
AiErken, NiJiati
Kuang, Xiaying
Zeng, Huijuan
Shao, Nan
Lin, Ying
Liu, Pian
Wang, Shenming
author_sort Ye, Runyi
collection PubMed
description Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER(+) breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer.
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spelling pubmed-84331332021-09-24 Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer Ye, Runyi AiErken, NiJiati Kuang, Xiaying Zeng, Huijuan Shao, Nan Lin, Ying Liu, Pian Wang, Shenming Oncogenesis Article Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins. However, the precise molecular mechanism and function of TRIM3 in SUMOylation and the response to tamoxifen remain unclear. In the present study, we observed that TRIM3 was dramatically overexpressed in breast cancer, which correlated with tamoxifen resistance. Furthermore, TRIM3 overexpression significantly correlated with poor survival of patients with ER(+) breast cancer treated with tamoxifen. TRIM3 overexpression conferred cell survival and tumorigenesis, whereas knocking down of TRIM3 reduced these capabilities. Moreover, TRIM3, as a ubiquitin carrier protein 9 (UBC9) binding protein, promoted SUMO modification of estrogen receptor 1 (ESR1) and activated the ER pathway. Silencing UBC9 abolished the function of TRIM3 in regulating tamoxifen resistance. These results suggest TRIM3 as a novel biomarker for breast cancer therapy, indicating that inhibiting TRIM3 combined with tamoxifen might provide a potential treatment for breast cancer. Nature Publishing Group UK 2021-09-10 /pmc/articles/PMC8433133/ /pubmed/34508066 http://dx.doi.org/10.1038/s41389-021-00350-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ye, Runyi
AiErken, NiJiati
Kuang, Xiaying
Zeng, Huijuan
Shao, Nan
Lin, Ying
Liu, Pian
Wang, Shenming
Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title_full Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title_fullStr Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title_full_unstemmed Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title_short Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer
title_sort tripartite motif-containing 3 (trim3) enhances er signaling and confers tamoxifen resistance in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433133/
https://www.ncbi.nlm.nih.gov/pubmed/34508066
http://dx.doi.org/10.1038/s41389-021-00350-x
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