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PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer

Triple-negative breast cancers (TNBCs) are the most aggressive breast cancers, and therapeutic options mainly rely on chemotherapy and immunotherapy. Although synthetic glucocorticoids (GCs) are given to alleviate the side effects of these treatments, GCs and their receptor, the glucocorticoid recep...

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Autores principales: Noureddine, Lara Malik, Ablain, Julien, Surmieliova-Garnès, Ausra, Jacquemetton, Julien, Pham, Thuy Ha, Marangoni, Elisabetta, Schnitzler, Anne, Bieche, Ivan, Badran, Bassam, Trédan, Olivier, Hussein, Nader, Le Romancer, Muriel, Poulard, Coralie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400884/
https://www.ncbi.nlm.nih.gov/pubmed/37536978
http://dx.doi.org/10.26508/lsa.202302009
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author Noureddine, Lara Malik
Ablain, Julien
Surmieliova-Garnès, Ausra
Jacquemetton, Julien
Pham, Thuy Ha
Marangoni, Elisabetta
Schnitzler, Anne
Bieche, Ivan
Badran, Bassam
Trédan, Olivier
Hussein, Nader
Le Romancer, Muriel
Poulard, Coralie
author_facet Noureddine, Lara Malik
Ablain, Julien
Surmieliova-Garnès, Ausra
Jacquemetton, Julien
Pham, Thuy Ha
Marangoni, Elisabetta
Schnitzler, Anne
Bieche, Ivan
Badran, Bassam
Trédan, Olivier
Hussein, Nader
Le Romancer, Muriel
Poulard, Coralie
author_sort Noureddine, Lara Malik
collection PubMed
description Triple-negative breast cancers (TNBCs) are the most aggressive breast cancers, and therapeutic options mainly rely on chemotherapy and immunotherapy. Although synthetic glucocorticoids (GCs) are given to alleviate the side effects of these treatments, GCs and their receptor, the glucocorticoid receptor (GR), were recently associated with detrimental effects, albeit the mechanisms involved remain elusive. Here, we identified the arginine methyltransferase PRMT5 as a master coregulator of GR, serving as a scaffold protein to recruit phospho-HP1γ and subsequently RNA polymerase II, independently of its methyltransferase activity. Moreover, the GR/PRMT5/HP1γ complex regulated the transcription of GC-target genes involved in cell motility and triggering cell migration of human TNBC cells in vitro and in a zebrafish model. Of note, we observed that GR/PRMT5 interaction was low in primary tumors but significantly increased in residual tumors treated with chemotherapy and GCs in neoadjuvant setting. These data suggest that the routine premedication prescription of GCs for early TNBC patients should be further assessed and that this complex could potentially be modulated to specifically target deleterious GR effects.
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spelling pubmed-104008842023-08-05 PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer Noureddine, Lara Malik Ablain, Julien Surmieliova-Garnès, Ausra Jacquemetton, Julien Pham, Thuy Ha Marangoni, Elisabetta Schnitzler, Anne Bieche, Ivan Badran, Bassam Trédan, Olivier Hussein, Nader Le Romancer, Muriel Poulard, Coralie Life Sci Alliance Research Articles Triple-negative breast cancers (TNBCs) are the most aggressive breast cancers, and therapeutic options mainly rely on chemotherapy and immunotherapy. Although synthetic glucocorticoids (GCs) are given to alleviate the side effects of these treatments, GCs and their receptor, the glucocorticoid receptor (GR), were recently associated with detrimental effects, albeit the mechanisms involved remain elusive. Here, we identified the arginine methyltransferase PRMT5 as a master coregulator of GR, serving as a scaffold protein to recruit phospho-HP1γ and subsequently RNA polymerase II, independently of its methyltransferase activity. Moreover, the GR/PRMT5/HP1γ complex regulated the transcription of GC-target genes involved in cell motility and triggering cell migration of human TNBC cells in vitro and in a zebrafish model. Of note, we observed that GR/PRMT5 interaction was low in primary tumors but significantly increased in residual tumors treated with chemotherapy and GCs in neoadjuvant setting. These data suggest that the routine premedication prescription of GCs for early TNBC patients should be further assessed and that this complex could potentially be modulated to specifically target deleterious GR effects. Life Science Alliance LLC 2023-08-03 /pmc/articles/PMC10400884/ /pubmed/37536978 http://dx.doi.org/10.26508/lsa.202302009 Text en © 2023 Noureddine et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Noureddine, Lara Malik
Ablain, Julien
Surmieliova-Garnès, Ausra
Jacquemetton, Julien
Pham, Thuy Ha
Marangoni, Elisabetta
Schnitzler, Anne
Bieche, Ivan
Badran, Bassam
Trédan, Olivier
Hussein, Nader
Le Romancer, Muriel
Poulard, Coralie
PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title_full PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title_fullStr PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title_full_unstemmed PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title_short PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
title_sort prmt5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400884/
https://www.ncbi.nlm.nih.gov/pubmed/37536978
http://dx.doi.org/10.26508/lsa.202302009
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