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The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness

Tumor metastasis profoundly reduces the survival of breast cancer patients, but the mechanisms underlying breast cancer invasiveness and metastasis are incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts in a sumoylation-dependent manner to suppress the invasive behavio...

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Autores principales: Chandhoke, Amrita Singh, Chanda, Ayan, Karve, Kunal, Deng, Lili, Bonni, Shirin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400561/
https://www.ncbi.nlm.nih.gov/pubmed/28423498
http://dx.doi.org/10.18632/oncotarget.15471
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author Chandhoke, Amrita Singh
Chanda, Ayan
Karve, Kunal
Deng, Lili
Bonni, Shirin
author_facet Chandhoke, Amrita Singh
Chanda, Ayan
Karve, Kunal
Deng, Lili
Bonni, Shirin
author_sort Chandhoke, Amrita Singh
collection PubMed
description Tumor metastasis profoundly reduces the survival of breast cancer patients, but the mechanisms underlying breast cancer invasiveness and metastasis are incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231 human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is required for sumoylated Smurf2 to suppress the invasive growth of breast cancer-cell derived organoids. Collectively, our findings define a novel role for the PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell invasiveness. These findings lay the foundation for the development of novel biomarkers and targeted therapeutic approaches in breast cancer.
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spelling pubmed-54005612017-05-03 The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness Chandhoke, Amrita Singh Chanda, Ayan Karve, Kunal Deng, Lili Bonni, Shirin Oncotarget Research Paper Tumor metastasis profoundly reduces the survival of breast cancer patients, but the mechanisms underlying breast cancer invasiveness and metastasis are incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231 human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is required for sumoylated Smurf2 to suppress the invasive growth of breast cancer-cell derived organoids. Collectively, our findings define a novel role for the PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell invasiveness. These findings lay the foundation for the development of novel biomarkers and targeted therapeutic approaches in breast cancer. Impact Journals LLC 2017-02-18 /pmc/articles/PMC5400561/ /pubmed/28423498 http://dx.doi.org/10.18632/oncotarget.15471 Text en Copyright: © 2017 Chandhoke et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Chandhoke, Amrita Singh
Chanda, Ayan
Karve, Kunal
Deng, Lili
Bonni, Shirin
The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title_full The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title_fullStr The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title_full_unstemmed The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title_short The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
title_sort pias3-smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400561/
https://www.ncbi.nlm.nih.gov/pubmed/28423498
http://dx.doi.org/10.18632/oncotarget.15471
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