机敏激素信号促进乳腺祖细胞扩增和乳腺癌风险

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-01-04 DOI:10.1016/j.stem.2023.12.002
Jason J. Northey, Mary-Kate Hayward, Yoshihiro Yui, Connor Stashko, FuiBoon Kai, Janna K. Mouw, Dhruv Thakar, Jonathon N. Lakins, Alastair J. Ironside, Susan Samson, Rita A. Mukhtar, E. Shelley Hwang, Valerie M. Weaver
{"title":"机敏激素信号促进乳腺祖细胞扩增和乳腺癌风险","authors":"Jason J. Northey, Mary-Kate Hayward, Yoshihiro Yui, Connor Stashko, FuiBoon Kai, Janna K. Mouw, Dhruv Thakar, Jonathon N. Lakins, Alastair J. Ironside, Susan Samson, Rita A. Mukhtar, E. Shelley Hwang, Valerie M. Weaver","doi":"10.1016/j.stem.2023.12.002","DOIUrl":null,"url":null,"abstract":"<p><span>Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression, but tissue-specific factors linking these associations remain ill-defined. We observed that stiff breast tissue from women with high mammographic density, who exhibit increased lifetime risk for breast cancer, associates with abundant stem-progenitor epithelial cells. Using genetically engineered mouse<span><span> models of elevated integrin<span> mechanosignaling and collagen density, </span></span>syngeneic<span> manipulations, and spheroid<span> models, we determined that a stiff matrix and high mechanosignaling increase mammary epithelial stem-progenitor cell frequency and enhance tumor initiation </span></span></span></span><em>in vivo</em>. Augmented tissue mechanics expand stemness by potentiating extracellular signal-related kinase (ERK) activity to foster progesterone receptor-dependent RANK signaling. Consistently, we detected elevated phosphorylated ERK and progesterone receptors and increased levels of RANK signaling in stiff breast tissue from women with high mammographic density. The findings link fibrosis and mechanosignaling to stem-progenitor cell frequency and breast cancer risk and causally implicate epidermal growth factor receptor-ERK-dependent hormone signaling in this phenotype.</p>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":null,"pages":null},"PeriodicalIF":19.8000,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk\",\"authors\":\"Jason J. Northey, Mary-Kate Hayward, Yoshihiro Yui, Connor Stashko, FuiBoon Kai, Janna K. Mouw, Dhruv Thakar, Jonathon N. Lakins, Alastair J. Ironside, Susan Samson, Rita A. Mukhtar, E. Shelley Hwang, Valerie M. Weaver\",\"doi\":\"10.1016/j.stem.2023.12.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><span>Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression, but tissue-specific factors linking these associations remain ill-defined. We observed that stiff breast tissue from women with high mammographic density, who exhibit increased lifetime risk for breast cancer, associates with abundant stem-progenitor epithelial cells. Using genetically engineered mouse<span><span> models of elevated integrin<span> mechanosignaling and collagen density, </span></span>syngeneic<span> manipulations, and spheroid<span> models, we determined that a stiff matrix and high mechanosignaling increase mammary epithelial stem-progenitor cell frequency and enhance tumor initiation </span></span></span></span><em>in vivo</em>. Augmented tissue mechanics expand stemness by potentiating extracellular signal-related kinase (ERK) activity to foster progesterone receptor-dependent RANK signaling. Consistently, we detected elevated phosphorylated ERK and progesterone receptors and increased levels of RANK signaling in stiff breast tissue from women with high mammographic density. The findings link fibrosis and mechanosignaling to stem-progenitor cell frequency and breast cancer risk and causally implicate epidermal growth factor receptor-ERK-dependent hormone signaling in this phenotype.</p>\",\"PeriodicalId\":9665,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.8000,\"publicationDate\":\"2024-01-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2023.12.002\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2023.12.002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

摘要

组织干祖细胞频率与肿瘤风险和进展有关,但与这些关联相关的组织特异性因素仍不明确。我们观察到,乳房X线照相术密度高的女性终生罹患乳腺癌的风险增加,她们的僵硬乳房组织与丰富的干祖细胞上皮细胞有关。利用整合素机械信号传导和胶原蛋白密度升高的基因工程小鼠模型、合成操作和球体模型,我们确定了坚硬的基质和高机械信号传导会增加乳腺上皮干祖细胞的频率,并增强体内肿瘤的发生。增强的组织力学通过增强细胞外信号相关激酶(ERK)的活性来促进依赖于孕酮受体的RANK信号传导,从而扩大干细胞的数量。同样,我们在高乳腺密度女性的僵硬乳腺组织中检测到磷酸化ERK和孕酮受体升高,以及RANK信号水平升高。这些发现将纤维化和机械信号转导与干祖细胞频率和乳腺癌风险联系起来,并将表皮生长因子受体-ERK依赖性激素信号转导与这种表型有因果关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk

Tissue stem-progenitor cell frequency has been implicated in tumor risk and progression, but tissue-specific factors linking these associations remain ill-defined. We observed that stiff breast tissue from women with high mammographic density, who exhibit increased lifetime risk for breast cancer, associates with abundant stem-progenitor epithelial cells. Using genetically engineered mouse models of elevated integrin mechanosignaling and collagen density, syngeneic manipulations, and spheroid models, we determined that a stiff matrix and high mechanosignaling increase mammary epithelial stem-progenitor cell frequency and enhance tumor initiation in vivo. Augmented tissue mechanics expand stemness by potentiating extracellular signal-related kinase (ERK) activity to foster progesterone receptor-dependent RANK signaling. Consistently, we detected elevated phosphorylated ERK and progesterone receptors and increased levels of RANK signaling in stiff breast tissue from women with high mammographic density. The findings link fibrosis and mechanosignaling to stem-progenitor cell frequency and breast cancer risk and causally implicate epidermal growth factor receptor-ERK-dependent hormone signaling in this phenotype.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
期刊最新文献
CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity All roads lead to cholesterol: Modulating lipid biosynthesis in multiple sclerosis patient-derived models Trained immunity in the bone marrow: Hub of autoimmunity To BE or to PE: Prime editors provide more choices for epitope-editing-based immunotherapy Nurturing protectors: Macrophages in the human pancreatic islet
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1