Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-15 DOI:10.1038/s41467-025-64255-8

Michael F Ciccone,Dhivyaa Anandan,Deeptiman Chatterjee,Chen Chen,Marygrace C Trousdell,Rebecca Anderson,Steven M Lewis,Mackenzie K Callaway,Chris Z Zhao,Amritha Varshini Hanasoge Somasundara,Suzanne Russo,Shih-Ting Yang,Yixin Zhao,Julie Ostrander,John E Wilkinson,William C K Pomerantz,Adam Siepel,David L Spector,Jessica Tollkuhn,Camila O Dos Santos

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Abstract

Context-specific epigenetic dependencies, shaped by chromatin remodeling can create exploitable vulnerabilities for cancer therapies that are unique to tissue types and cellular identities. Here, we show that loss of BPTF (Bromodomain PHD Finger Transcription Factor), a core component of the NURF (Nucleosome Remodeling Factor) complex, results in the emergence of estrogen-responsive, tamoxifen-sensitive, Estrogen Receptor alpha (ERα) positive mammary tumors without altering cancer cell state and tumor pathology. Elevated ERα levels in BPTFKO mammary tumor cells are linked with decreased TGF-β activity and limited metastatic spread of mammary tumor cells to the lungs. Loss of ERα is sufficient to restore TGF-β activity and the metastatic potential in BPTFKO tumors. These findings highlight a mechanism through which BPTF regulates tumor development and progression in mammary epithelial cells, offering insights into the interplay between chromatin remodeling, estrogen signaling, and their resultant adjuvant therapeutic potential in breast cancer.

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BPTF的缺失恢复雌激素反应并抑制乳腺肿瘤的转移。

由染色质重塑形成的环境特异性表观遗传依赖性可以为组织类型和细胞身份独特的癌症治疗创造可利用的脆弱性。本研究表明，核小体重塑因子复合体的核心组成部分Bromodomain PHD手指转录因子（BPTF）的缺失会导致雌激素应答、他莫昔芬敏感、雌激素受体α (ERα)阳性乳腺肿瘤的出现，而不会改变癌细胞状态和肿瘤病理。BPTFKO乳腺肿瘤细胞中ERα水平升高与TGF-β活性降低和乳腺肿瘤细胞向肺转移扩散受限有关。ERα的缺失足以恢复BPTFKO肿瘤中TGF-β的活性和转移潜能。这些发现强调了BPTF调节乳腺上皮细胞肿瘤发生和进展的机制，为染色质重塑、雌激素信号传导及其在乳腺癌辅助治疗中的潜在作用提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.