Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785084538635943936 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10400884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT noureddinelaramalik prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT ablainjulien prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT surmieliovagarnesausra prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT jacquemettonjulien prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT phamthuyha prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT marangonielisabetta prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT schnitzleranne prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT biecheivan prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT badranbassam prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT tredanolivier prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT husseinnader prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT leromancermuriel prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer AT poulardcoralie prmt5triggersglucocorticoidinducedcellmigrationintriplenegativebreastcancer |