Nuclear PRMT5 is a biomarker of sensitivity to tamoxifen in ERα
Humans
Female
Tamoxifen
/ pharmacology
Breast Neoplasms
/ pathology
Estrogen Receptor alpha
/ genetics
Signal Transduction
Biomarkers
Drug Resistance, Neoplasm
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Antineoplastic Agents, Hormonal
/ pharmacology
Protein-Arginine N-Methyltransferases
/ metabolism
PRMT5
arginine methylation
estrogen receptor
resistance
tamoxifen
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 08 2023
07 08 2023
Historique:
revised:
23
06
2023
received:
13
02
2023
accepted:
26
06
2023
medline:
8
8
2023
pubmed:
17
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Endocrine therapies targeting estrogen signaling, such as tamoxifen, have significantly improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, their efficacy is limited by intrinsic and acquired resistance to treatment, and there is currently no predictive marker of response to these anti-estrogens to guide treatment decision. Here, using two independent cohorts of breast cancer patients, we identified nuclear PRMT5 expression as an independent predictive marker of sensitivity to tamoxifen. Mechanistically, we discovered that tamoxifen stimulates ERα methylation by PRMT5, a key event for its binding to corepressors such as SMRT and HDAC1, participating in the inhibition of the transcriptional activity of ERα. Although PRMT5 is mainly localized in the cytoplasm of tumor cells, our analyses show that tamoxifen triggers its nuclear translocation in tamoxifen-sensitive tumors but not in resistant ones. Hence, we unveil a biomarker of sensitivity to tamoxifen in ERα-positive breast tumors that could be used to enhance the response of breast cancer patients to endocrine therapy, by fostering its nuclear expression.
Identifiants
pubmed: 37458145
doi: 10.15252/emmm.202217248
pmc: PMC10405064
doi:
Substances chimiques
Tamoxifen
094ZI81Y45
Estrogen Receptor alpha
0
Biomarkers
0
Antineoplastic Agents, Hormonal
0
PRMT5 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e17248Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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