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MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α

Breast cancer is the most commonly diagnosed malignant tumor among females. Estrogen receptor α (ERα) is initially expressed in 70% of breast cancers and is a well-known target of endocrine therapy for ERα-positive breast cancer. In the present study, we identified MINDY1, a member belongs to the mo...

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Autores principales: Tang, Jianing, Luo, Yongwen, Long, Guo, Zhou, Ledu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514509/
https://www.ncbi.nlm.nih.gov/pubmed/34645792
http://dx.doi.org/10.1038/s41419-021-04244-z
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author Tang, Jianing
Luo, Yongwen
Long, Guo
Zhou, Ledu
author_facet Tang, Jianing
Luo, Yongwen
Long, Guo
Zhou, Ledu
author_sort Tang, Jianing
collection PubMed
description Breast cancer is the most commonly diagnosed malignant tumor among females. Estrogen receptor α (ERα) is initially expressed in 70% of breast cancers and is a well-known target of endocrine therapy for ERα-positive breast cancer. In the present study, we identified MINDY1, a member belongs to the motif interacting with Ubcontaining novel DUB family (MINDY), as a potential deubiquitylase of ERα in breast cancer. There was a positive correlation between ERα and MINDY1 protein levels in human breast cancer tissues. We found that high expression of MINDY1 was associated with poor prognosis. MINDY1 interacted with ERα, thereby mediating the deubiquitination of ERα and increased its stability in a deubiquitylation activity-dependent manner. MINDY1 depletion significantly decreased the ERα protein level and ERα signaling activity in breast cancer cells. Specifically, MINDY1 associated with the N-terminal of ERα via its catalytic domain, thus inhibiting K48-specific poly-ubiquitination process on ERα protein. In addition, MINDY1 depletion led to growth inhibition and cell cycle arrest of ERα-positive breast cancer cells. Finally, overexpression of ERα could rescue the MINDY1 depletion-induced growth inhibition both in vitro and in vivo, suggesting that MINDY1 promotes breast carcinogenesis through increasing ERα stability. Overall, our study proposed a novel post-translational mechanism of ERα in supporting breast cancer progression. Targeting the MINDY1 may prove to be a promising strategy for patients with ERα-positive breast cancer.
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spelling pubmed-85145092021-10-29 MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α Tang, Jianing Luo, Yongwen Long, Guo Zhou, Ledu Cell Death Dis Article Breast cancer is the most commonly diagnosed malignant tumor among females. Estrogen receptor α (ERα) is initially expressed in 70% of breast cancers and is a well-known target of endocrine therapy for ERα-positive breast cancer. In the present study, we identified MINDY1, a member belongs to the motif interacting with Ubcontaining novel DUB family (MINDY), as a potential deubiquitylase of ERα in breast cancer. There was a positive correlation between ERα and MINDY1 protein levels in human breast cancer tissues. We found that high expression of MINDY1 was associated with poor prognosis. MINDY1 interacted with ERα, thereby mediating the deubiquitination of ERα and increased its stability in a deubiquitylation activity-dependent manner. MINDY1 depletion significantly decreased the ERα protein level and ERα signaling activity in breast cancer cells. Specifically, MINDY1 associated with the N-terminal of ERα via its catalytic domain, thus inhibiting K48-specific poly-ubiquitination process on ERα protein. In addition, MINDY1 depletion led to growth inhibition and cell cycle arrest of ERα-positive breast cancer cells. Finally, overexpression of ERα could rescue the MINDY1 depletion-induced growth inhibition both in vitro and in vivo, suggesting that MINDY1 promotes breast carcinogenesis through increasing ERα stability. Overall, our study proposed a novel post-translational mechanism of ERα in supporting breast cancer progression. Targeting the MINDY1 may prove to be a promising strategy for patients with ERα-positive breast cancer. Nature Publishing Group UK 2021-10-13 /pmc/articles/PMC8514509/ /pubmed/34645792 http://dx.doi.org/10.1038/s41419-021-04244-z Text en © The Author(s) 2021, corrected publication 2022 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
Tang, Jianing
Luo, Yongwen
Long, Guo
Zhou, Ledu
MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title_full MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title_fullStr MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title_full_unstemmed MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title_short MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
title_sort mindy1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514509/
https://www.ncbi.nlm.nih.gov/pubmed/34645792
http://dx.doi.org/10.1038/s41419-021-04244-z
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