Nuclear <scp>PRMT5</scp> is a biomarker of sensitivity to tamoxifen in <scp>ERα</scp><sup>+</sup> breast cancer - CRCL-Résistance hormonale, méthylation et cancer du sein Access content directly
Journal Articles EMBO Molecular Medicine Year : 2023

Nuclear PRMT5 is a biomarker of sensitivity to tamoxifen in ERα+ breast cancer

Youenn Drouet
Loay Kassem
Jonathan Reboulet
Elisabetta Marangoni

Abstract

Endocrine therapies targeting estrogen signaling, such as tamoxifen, have significantly improved management of estrogen receptor alpha (ERa)-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 ERa 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 ERa. 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 ERa-positive breast tumors that could be used to enhance the response of breast cancer patients to endocrine therapy, by fostering its nuclear expression.
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Dates and versions

hal-04382544 , version 1 (09-01-2024)

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Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, et al.. Nuclear PRMT5 is a biomarker of sensitivity to tamoxifen in ERα+ breast cancer. EMBO Molecular Medicine, 2023, 15, ⟨10.15252/emmm.202217248⟩. ⟨hal-04382544⟩
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