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This study reports that CREPT/RPRD1B, amplified at the somatic copy-number level and upregulated, associates with poor survival and actively drives TNBC metastasis. CREPT reshapes three-dimensional genome architecture by promoting co-operational chromatin loops that coordinate RNAPII loading and recycling to boost metastatic gene expression. Disrupting loops via CRISPR-dCas9 or depleting CREPT with AAV-based shRNA suppresses metastasis in vivo.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/crept-is-required-for-the-metastasis-of-triple-negative-breast-cancer-through-a-co-operational-chromatin-loop-based-gene-regulation/376138/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/crept-is-required-for-the-metastasis-of-triple-negative-breast-cancer-through-a-co-operational-chromatin-loop-based-gene-regulation/376138.png","ImageObject",300,407,{"name":92,"@type":93},"Adam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the reported role of CREPT in TNBC metastasis?","Question",{"text":112,"@type":113},"CREPT/RPRD1B is amplified and upregulated in TNBC and drives metastatic progression by regulating genome structure and chromatin loops that enhance metastatic gene expression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does CREPT influence genome organization?",{"text":117,"@type":113},"CREPT occupies promoters and enhancers to alter three-dimensional genome structures, organizing co-operational chromatin loops in TAD status and chromatin-loop configurations.",{"name":119,"@type":110,"acceptedAnswer":120},"What experimental strategies suppress TNBC metastasis based on these findings?",{"text":121,"@type":113},"Disrupting the co-operational chromatin loops using CRISPR-dCas9 suppresses TNBC metastasis in vivo, and AAV-based shRNA depletion of CREPT blocks metastasis in both preventative and therapeutic mouse models.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},376138,1790489233,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":36,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1374404737137,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Li et al. Molecular Cancer (2025) 24:170 [https://doi.org/10.1186/s12943-025-02361-3](https://doi.org/10.1186/s12943-025-02361-3)  \nMolecular Cancer  \n RESEARCH Open Access  \nCREPT is required for the metastasis  \nof triple-negative breast cancer  \nthrough a co-operational-chromatin loop-based gene regulation  \nJianghua Li1, Lu Xu1,2, Jiayu Wang1, Xuning Wang3, Yuting Lin1, Alex Yutian Zou4, Fangli Ren1, Yinyin Wang1*, Jun Li5* and Zhijie Chang1*  \nAbstract  \nTriple-negative breast cancer (TNBC) is recognized for its aggressiveness, yet the mechanism underlying metastasis remains unclear. Here, we report that CREPT/RPRD1B, which exhibits somatic gene copy-number amplifications and elevated expression, correlates with poor patient survival and drivesTNBC metastasis. We demonstrate that CREPT alters three-dimensional genome structures in topologically-associating domain (TAD) status and chromatin loops via occupying promoters and enhancers. Specifically, CREPT mediates 1082 co-operational chromatin loops configured by enhancer-promoter and promoter-termination loops, which are validated by HiChIP analyses and visualized by Tn5-FISH experiments. These loops orchestrate RNAPII loading and recycling to enhance the metastatic gene expression. Disruption of these co-operational loops using CRISPR-dCas9 suppressesTNBC metastasis in vivo. Furthermore, depletion of CREPT using an AAV-based shRNA blocksTNBC metastasis in both preventative and therapeutic mouse models. We propose that targeting CREPT to disrupt the co-operational chromatin loop structures represents a promising therapeutic strategy for metastatic TNBC.  \nHighlights  \n• Somatic CREPT gene copy-number amplifications with elevated expression occur in the metastatic triple-negative breast cancer (TNBC) and correlate with poor patient survival  \n• CREPT mediates 1082 co-operational chromatin loops configured by enhancer-promoter and promoter-termination loops  \n• CREPT-mediated co-operational chromatin loops regulate metastatic genes during the metastasis ofTNBC  \n• Depleting CREPT by adeno-associated virus (AAV) blocksTNBC metastasis in preventative and therapeutic mouse models  \n*Correspondence:  \nYinyin Wang [wangyinyin@mail.tsinghua.edu.cn](wangyinyin@mail.tsinghua.edu.cn)[ ](wangyinyin@mail.tsinghua.edu.cn)Jun Li  \n[junlibenben@163.com](junlibenben@163.com)  \nZhijie Chang [zhijiec@tsinghua.edu.cn](zhijiec@tsinghua.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nLi etal. Molecular Cancer (2025) 24:170 Page 2 of 40  \nGraphical Abstract  \nIntroduction  \nTriple-negative breastcancer (TNBC) is a highly malignant disease characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) with no amplification of human epithelial growth factor receptor 2 (HER2) [1, 2]. The disease often progres","cbCaibiZyZ25uiJe","https://ap.wps.com/l/cbCaibiZyZ25uiJe","pdf",17703538,"English","# Abstract\n# Highlights\n# Introduction","[{\"question\":\"What is the reported role of CREPT in TNBC metastasis?\",\"answer\":\"CREPT/RPRD1B is amplified and upregulated in TNBC and drives metastatic progression by regulating genome structure and chromatin loops that enhance metastatic gene expression.\"},{\"question\":\"How does CREPT influence genome organization?\",\"answer\":\"CREPT occupies promoters and enhancers to alter three-dimensional genome structures, organizing co-operational chromatin loops in TAD status and chromatin-loop configurations.\"},{\"question\":\"What experimental strategies suppress TNBC metastasis based on these findings?\",\"answer\":\"Disrupting the co-operational chromatin loops using CRISPR-dCas9 suppresses TNBC metastasis in vivo, and AAV-based shRNA depletion of CREPT blocks metastasis in both preventative and therapeutic mouse models.\"}]","CREPT is required for the metastasis of triple-negative breast cancer through a co-operational-chromatin loop-based gene regulation | PDF",1790217438,101]