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This study uses a microfluidic device to generate doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by creating gradients of DOX and medium. In vivo chemoresistant xenografts, genome-wide transcriptomics, and patient tissue analyses indicate chemoresistance results from failed epigenetic control of the NUPR1/HDAC11 axis, with high NUPR1 predicting poor clinical outcomes. The microfluidic approach rapidly induces resistant cells that may enhance tumor heterogeneity and chemoresistance, supporting further study of NUPR1/HDAC11 epigenetic regulation in TNBC.",{"@graph":69,"@context":123},[70,84,106],{"@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/exploration-of-drug-resistance-mechanisms-in-triple-negative-breast-cancer-cells-using-a-microfluidic-device-and-patient-tissues/330357/",{"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/exploration-of-drug-resistance-mechanisms-in-triple-negative-breast-cancer-cells-using-a-microfluidic-device-and-patient-tissues/330357.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How were doxorubicin-resistant TNBC cells generated in this research?","Question",{"text":113,"@type":114},"A Cancer Drug Resistance Accelerator (CDRA) microfluidic chip was used to create gradients of doxorubicin (DOX) and medium, inducing DOX-resistant (DOXR) cells from MDA-MB-231 TNBC cells within 11 days.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What molecular mechanism was implicated in chemoresistance?",{"text":118,"@type":114},"Chemoresistance was linked to failed epigenetic control of the NUPR1/HDAC11 axis, and elevated NUPR1 expression correlated with poor clinical outcomes.",{"name":120,"@type":111,"acceptedAnswer":121},"What evidence supported the conclusions beyond cell-based experiments?",{"text":122,"@type":114},"The study reports supporting findings from in vivo chemoresistant xenograft models, unbiased genome-wide transcriptome analysis, and patient tissue/data analyses.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},330357,1790018276,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","RESEARCH ARTICLE  \n*For correspondence:  \n[jeeahn@skku.edu](jeeahn@skku.edu) (JYA); [nanopark@skku.edu](nanopark@skku.edu) (SP)  \n†These authors contributed equally to this work  \nCompeting interest: The authors declare that no competing interests exist.  \nFunding: See page 14  \nSent for Review  \n09 May 2023  \nPreprint posted  \n24 May 2023  \nReviewed preprint posted  \n03 October 2023  \nReviewed preprint revised  \n28 February 2024  \nVersion of Record published  \n27 March 2024  \nReviewing Editor: Goutham Narla, University of Michigan– Ann Arbor, United States  \n Copyright Lim, Hwanget al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.  \nExploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues  \nWanyoung Lim1†, Inwoo Hwang2†, Jiande Zhang3, Zhenzhong Chen3, Jeonghun Han3, Jaehyung Jeon3, Bon-Kyoung Koo4, Sangmin Kim5, Jeong Eon Lee6, Youngkwan Kim2, Kenneth J Pienta7, Sarah R Amend7, Robert H Austin8, Jee-Yin Ahn2,9,10*, Sungsu Park1,3,11*  \n1 Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea; 2 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; 3School of Mechanical Engineering, Sungkyunkwan University, Suwon, Republic of Korea; 4 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria; 5 Department of Breast Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6 Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 7The Cancer Ecology Center at the James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, United States; 8 Department of Physics, Princeton University, Princeton, United States; 9Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; 10Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 11 Institute of Quantum Biophysics (IQB), Sungkyunkwan University, Suwon, Republic of Korea  \nAbstract Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/ HDAC11 axis in TNBC.  \neLife assessment  \nThis study based on the use of Cancer Drug Resistance Accelerator (CDRA) chip is valuable as a platform technology to assess chemoresistance mechanisms. The strength is convincing from the technological point of view. However, the use of a single cell line model is a limitation. However we  \nLim, Hwang et al. eLife 2023;12:RP88830. DOI: [https://doi.org/10.7554/eLife.88830](https://doi.org/10.7554/eLife.88830) 1 of 18  \n Research article Cancer Biology  \nacknowledge the authors' plan to further validate their current findings across multiple TNBC cell lines.  \nIntroduction  \nA","cbCaiawwzknz6BSb","https://ap.wps.com/l/cbCaiawwzknz6BSb","pdf",9052112,18,"English","# Introduction\n## Microfluidic chips for studying drug resistance\n## Purpose and approach of the study","[{\"question\":\"How were doxorubicin-resistant TNBC cells generated in this research?\",\"answer\":\"A Cancer Drug Resistance Accelerator (CDRA) microfluidic chip was used to create gradients of doxorubicin (DOX) and medium, inducing DOX-resistant (DOXR) cells from MDA-MB-231 TNBC cells within 11 days.\"},{\"question\":\"What molecular mechanism was implicated in chemoresistance?\",\"answer\":\"Chemoresistance was linked to failed epigenetic control of the NUPR1/HDAC11 axis, and elevated NUPR1 expression correlated with poor clinical outcomes.\"},{\"question\":\"What evidence supported the conclusions beyond cell-based experiments?\",\"answer\":\"The study reports supporting findings from in vivo chemoresistant xenograft models, unbiased genome-wide transcriptome analysis, and patient tissue/data analyses.\"}]","Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues | PDF",1789988437,45]