• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

组蛋白去乙酰化酶抑制剂诱导 LIFR 表达并促进乳腺癌休眠表型。

HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer.

机构信息

Program in Cancer Biology, Vanderbilt University, Nashville, TN, USA.

Vanderbilt Center for Bone Biology, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

出版信息

Oncogene. 2021 Aug;40(34):5314-5326. doi: 10.1038/s41388-021-01931-1. Epub 2021 Jul 10.

DOI:10.1038/s41388-021-01931-1
PMID:34247191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8403155/
Abstract

Despite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. Leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells and LIFR loss is correlated with poor patient survival. Herein, we demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. Primary breast tumors from HDACi-treated patients had increased LIFR levels and reduced proliferation rates compared to pre-treatment levels. Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.

摘要

尽管乳腺癌治疗取得了进展，但休眠肿瘤细胞驱动的残留疾病仍然是一个重大的临床问题。白血病抑制因子受体 (LIFR) 促进乳腺癌细胞的休眠表型，而 LIFR 的缺失与患者预后不良相关。在此，我们证明组蛋白去乙酰化酶抑制剂（HDACi）在乳腺癌的 III 期临床试验中，通过表观遗传诱导 LIFR 并激活乳腺癌细胞的休眠前程序。HDACi 减缓了乳腺癌细胞的增殖并减少了原发性肿瘤的生长。与治疗前水平相比，接受 HDACi 治疗的患者的原发性乳腺肿瘤中 LIFR 水平升高，增殖速度降低。最近一项关于转移性乳腺癌中恩替诺特和阿扎胞苷的 II 期临床试验数据表明，治疗后诱导几个休眠前基因与患者的生存时间延长有关。总之，这些发现表明 HDACi 是一种有潜力的治疗方法，可以促进休眠、预防复发，并改善乳腺癌患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/1903ed0d8791/nihms-1719718-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/e2b7652be168/nihms-1719718-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/be06b453261b/nihms-1719718-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/d50fd0b8da3d/nihms-1719718-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/9b6fcadae7a1/nihms-1719718-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/68ec8242159f/nihms-1719718-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/1903ed0d8791/nihms-1719718-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/e2b7652be168/nihms-1719718-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/be06b453261b/nihms-1719718-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/d50fd0b8da3d/nihms-1719718-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/9b6fcadae7a1/nihms-1719718-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/68ec8242159f/nihms-1719718-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b2/8403155/1903ed0d8791/nihms-1719718-f0006.jpg

相似文献

1
HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer.组蛋白去乙酰化酶抑制剂诱导 LIFR 表达并促进乳腺癌休眠表型。
Oncogene. 2021 Aug;40(34):5314-5326. doi: 10.1038/s41388-021-01931-1. Epub 2021 Jul 10.
2
Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer.反馈：白血病抑制因子受体的激活限制了乳腺癌对组蛋白去乙酰化酶抑制剂的反应。
Cancer Cell. 2016 Sep 12;30(3):459-473. doi: 10.1016/j.ccell.2016.08.001.
3
Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer.组蛋白去乙酰化酶抑制剂通过NOXA介导的MCL1降解增强MEK抑制剂在三阴性和炎性乳腺癌中的疗效。
Clin Cancer Res. 2017 Aug 15;23(16):4780-4792. doi: 10.1158/1078-0432.CCR-16-2622. Epub 2017 May 2.
4
LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.LIFR 是 Hippo-YAP 通路的上游乳腺癌转移抑制因子和预后标志物。
Nat Med. 2012 Oct;18(10):1511-7. doi: 10.1038/nm.2940. Epub 2012 Sep 23.
5
LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer.LIFR 抑制增强了组蛋白去乙酰化酶抑制剂在三阴性乳腺癌中的治疗效果。
Commun Biol. 2021 Oct 29;4(1):1235. doi: 10.1038/s42003-021-02741-7.
6
HDAC inhibitors stimulate LIFR when it is repressed by hypoxia or PTHrP in breast cancer.在乳腺癌中，当LIFR被缺氧或甲状旁腺激素相关蛋白（PTHrP）抑制时，组蛋白去乙酰化酶（HDAC）抑制剂可刺激LIFR。
J Bone Oncol. 2021 Dec 1;31:100407. doi: 10.1016/j.jbo.2021.100407. eCollection 2021 Dec.
7
EGFR-upregulated LIFR promotes SUCLG2-dependent castration resistance and neuroendocrine differentiation of prostate cancer.表皮生长因子受体上调白细胞介素 6 受体信号通路促进前列腺癌去势抵抗和神经内分泌分化
Oncogene. 2020 Oct;39(44):6757-6775. doi: 10.1038/s41388-020-01468-9. Epub 2020 Sep 22.
8
HDAC Inhibition for the Treatment of Epithelioid Sarcoma: Novel Cross Talk Between Epigenetic Components.组蛋白去乙酰化酶抑制用于上皮样肉瘤的治疗：表观遗传成分之间的新型相互作用
Mol Cancer Res. 2016 Jan;14(1):35-43. doi: 10.1158/1541-7786.MCR-15-0295. Epub 2015 Sep 22.
9
LIFR promotes tumor angiogenesis by up-regulating IL-8 levels in colorectal cancer.LIFR 通过上调结直肠癌中 IL-8 的水平促进肿瘤血管生成。
Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2769-2784. doi: 10.1016/j.bbadis.2018.05.004. Epub 2018 May 9.
10
Epigenetic reactivation of estrogen receptor-α (ERα) by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancer.金雀异黄素通过表观遗传再激活雌激素受体-α（ERα）增强 ERα 阴性乳腺癌的激素治疗敏感性。
Mol Cancer. 2013 Feb 4;12:9. doi: 10.1186/1476-4598-12-9.

引用本文的文献

1
Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies.理解肿瘤休眠：从实验模型到机制与治疗策略
Biomol Ther (Seoul). 2025 Sep 1;33(5):770-784. doi: 10.4062/biomolther.2025.056. Epub 2025 Aug 31.
2
Decoding the adaptive survival mechanisms of breast cancer dormancy.解码乳腺癌休眠的适应性生存机制。
Oncogene. 2025 Aug 27. doi: 10.1038/s41388-025-03529-3.
3
Clinical applications of circulating tumor cells in metastasis and therapy.循环肿瘤细胞在转移和治疗中的临床应用

本文引用的文献

1
PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells.PREX1 驱动雌激素受体阳性乳腺癌细胞自发骨转移。
Oncogene. 2020 Feb;39(6):1318-1334. doi: 10.1038/s41388-019-1064-3. Epub 2019 Oct 21.
2
Breast Cancer Dormancy in Bone.骨中乳腺癌休眠
Curr Osteoporos Rep. 2019 Oct;17(5):353-361. doi: 10.1007/s11914-019-00532-y.
3
Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy.针对血管周围基质细胞使播散的肿瘤细胞对化疗更敏感。
J Hematol Oncol. 2025 Aug 22;18(1):80. doi: 10.1186/s13045-025-01733-y.
4
Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.弥合乳腺癌休眠的差距：模型、机制及转化挑战
Pharmaceuticals (Basel). 2025 Jun 26;18(7):961. doi: 10.3390/ph18070961.
5
Adaptation to acidic conditions that mimic the tumor microenvironment, downregulates miR-193b-3p, and induces EMT via TGFβ2 in A549 cells.适应模拟肿瘤微环境的酸性条件会下调A549细胞中的miR-193b-3p，并通过TGFβ2诱导上皮-间质转化。
PLoS One. 2025 Feb 24;20(2):e0318811. doi: 10.1371/journal.pone.0318811. eCollection 2025.
6
Towards understanding cancer dormancy over strategic hitching up mechanisms to technologies.通过将战略搭便车机制与技术相结合来理解癌症休眠。
Mol Cancer. 2025 Feb 14;24(1):47. doi: 10.1186/s12943-025-02250-9.
7
Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence.肿瘤休眠与复发：理解癌症复发的分子机制
Mil Med Res. 2025 Feb 11;12(1):7. doi: 10.1186/s40779-025-00595-2.
8
Cancer Cells in Sleep Mode: Wake Them to Eliminate or Keep Them Asleep Forever?处于睡眠模式的癌细胞：唤醒它们以消灭还是让它们永远沉睡？
Cells. 2024 Dec 6;13(23):2022. doi: 10.3390/cells13232022.
9
SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter.SNORA28 通过增加 LIFR 启动子上的 H3K9 乙酰化来促进结直肠癌细胞的增殖和放射抵抗，通过 STAT3 通路。
Adv Sci (Weinh). 2024 Aug;11(32):e2405332. doi: 10.1002/advs.202405332. Epub 2024 Jun 26.
10
PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.甲状旁腺激素相关蛋白的胞内作用通过 p27 和 LIFR 对乳腺癌的生长产生不同的影响。
Breast Cancer Res. 2024 Feb 26;26(1):34. doi: 10.1186/s13058-024-01791-z.
Nat Cell Biol. 2019 Feb;21(2):238-250. doi: 10.1038/s41556-018-0267-0. Epub 2019 Jan 21.
4
Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.组蛋白去乙酰化酶抑制剂（HDACi）联合疗法治疗癌症：实现HDACi的全部治疗潜力
Front Oncol. 2018 Mar 29;8:92. doi: 10.3389/fonc.2018.00092. eCollection 2018.
5
Osteoblast-Secreted Factors Mediate Dormancy of Metastatic Prostate Cancer in the Bone via Activation of the TGFβRIII-p38MAPK-pS249/T252RB Pathway.成骨细胞分泌因子通过激活 TGFβRIII-p38MAPK-pS249/T252RB 通路介转移前列腺癌在骨中的休眠。
Cancer Res. 2018 Jun 1;78(11):2911-2924. doi: 10.1158/0008-5472.CAN-17-1051. Epub 2018 Mar 7.
6
MSK1 regulates luminal cell differentiation and metastatic dormancy in ER breast cancer.MSK1 调控 ER 阳性乳腺癌腔细胞分化和转移休眠。
Nat Cell Biol. 2018 Feb;20(2):211-221. doi: 10.1038/s41556-017-0021-z. Epub 2018 Jan 22.
7
Association of FGFR1 with ERα Maintains Ligand-Independent ER Transcription and Mediates Resistance to Estrogen Deprivation in ER Breast Cancer.成纤维细胞生长因子受体 1（FGFR1）与雌激素受体α（ERα）的关联维持了配体非依赖性 ER 转录，并介导了 ER 阳性乳腺癌对雌激素剥夺的耐药性。
Clin Cancer Res. 2017 Oct 15;23(20):6138-6150. doi: 10.1158/1078-0432.CCR-17-1232. Epub 2017 Jul 27.
8
Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells.乙酰化和磷酸化在 LIFR 依赖的小鼠胚胎干细胞自我更新生长信号中的拮抗作用。
Cell Rep. 2017 Jan 24;18(4):933-946. doi: 10.1016/j.celrep.2016.12.081.
9
Tumor cell dormancy.肿瘤细胞休眠
Mol Oncol. 2017 Jan;11(1):62-78. doi: 10.1016/j.molonc.2016.09.009. Epub 2016 Oct 7.
10
Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study.5-氮杂胞苷与恩替诺特联合用于晚期乳腺癌的表观遗传治疗：一项美国国立癌症研究所/勇敢抗癌组织的II期研究。
Clin Cancer Res. 2017 Jun 1;23(11):2691-2701. doi: 10.1158/1078-0432.CCR-16-1729. Epub 2016 Dec 15.