Cargando…
Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1
Estrogen receptor α (ERα) is the major driver for breast tumor carcinogenesis and progression, while ERα positive breast cancer is the major subtype in breast malignancies, which account for 70% breast cancers in patients. The success of endocrine therapy such as tamoxifen is one of the biggest brea...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173209/ https://www.ncbi.nlm.nih.gov/pubmed/34094957 http://dx.doi.org/10.3389/fonc.2021.664689 |
_version_ | 1783702679833280512 |
---|---|
author | Ding, Jianing Kuang, Peng |
author_facet | Ding, Jianing Kuang, Peng |
author_sort | Ding, Jianing |
collection | PubMed |
description | Estrogen receptor α (ERα) is the major driver for breast tumor carcinogenesis and progression, while ERα positive breast cancer is the major subtype in breast malignancies, which account for 70% breast cancers in patients. The success of endocrine therapy such as tamoxifen is one of the biggest breakthroughs in breast cancer treatments. However, the endocrine therapy resistance is a headache problem in breast cancer. Further mechanisms need to be identified to the effect of ERα signaling in controlling breast cancer progression and drug resistance. HOIL-1 was firstly identified as the ERα transcriptional co-activator in modulating estrogen signaling in breast cancer. In our current study, we showed that HOIL-1, which was elevated in breast cancer, related to good prognosis in ERα positive breast cancer, but correlated with poor outcome in endocrine-treated patients. HOIL-1 was required for ERα positive breast cancer proliferation and clone formation, which effect could be rescued by further ERα overexpression. Further mechanism studies showed that HOIL-1 is required for ERα signaling activity in breast cancer cells. HOIL-1 could interact with ERα in the cytosol and modulate ERα stability via inhibiting ERα K48-linked poly-ubiquitination. Thus, our study demonstrated a novel post-translational modification in ERα signaling, which could provide novel strategy for ERα-driven breast cancer therapy. |
format | Online Article Text |
id | pubmed-8173209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81732092021-06-04 Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 Ding, Jianing Kuang, Peng Front Oncol Oncology Estrogen receptor α (ERα) is the major driver for breast tumor carcinogenesis and progression, while ERα positive breast cancer is the major subtype in breast malignancies, which account for 70% breast cancers in patients. The success of endocrine therapy such as tamoxifen is one of the biggest breakthroughs in breast cancer treatments. However, the endocrine therapy resistance is a headache problem in breast cancer. Further mechanisms need to be identified to the effect of ERα signaling in controlling breast cancer progression and drug resistance. HOIL-1 was firstly identified as the ERα transcriptional co-activator in modulating estrogen signaling in breast cancer. In our current study, we showed that HOIL-1, which was elevated in breast cancer, related to good prognosis in ERα positive breast cancer, but correlated with poor outcome in endocrine-treated patients. HOIL-1 was required for ERα positive breast cancer proliferation and clone formation, which effect could be rescued by further ERα overexpression. Further mechanism studies showed that HOIL-1 is required for ERα signaling activity in breast cancer cells. HOIL-1 could interact with ERα in the cytosol and modulate ERα stability via inhibiting ERα K48-linked poly-ubiquitination. Thus, our study demonstrated a novel post-translational modification in ERα signaling, which could provide novel strategy for ERα-driven breast cancer therapy. Frontiers Media S.A. 2021-05-20 /pmc/articles/PMC8173209/ /pubmed/34094957 http://dx.doi.org/10.3389/fonc.2021.664689 Text en Copyright © 2021 Ding and Kuang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ding, Jianing Kuang, Peng Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title | Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title_full | Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title_fullStr | Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title_full_unstemmed | Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title_short | Regulation of ERα Stability and Estrogen Signaling in Breast Cancer by HOIL-1 |
title_sort | regulation of erα stability and estrogen signaling in breast cancer by hoil-1 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173209/ https://www.ncbi.nlm.nih.gov/pubmed/34094957 http://dx.doi.org/10.3389/fonc.2021.664689 |
work_keys_str_mv | AT dingjianing regulationoferastabilityandestrogensignalinginbreastcancerbyhoil1 AT kuangpeng regulationoferastabilityandestrogensignalinginbreastcancerbyhoil1 |