[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-405555-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-405555-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","commd3-loss-drives-invasive-breast-cancer-growth-by-modulating-copper-homeostasis","COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis","","Despite improved breast cancer outcomes from earlier diagnosis and personalized treatment, some patients still develop recurrence and incurable metastases, highlighting the need to clarify molecular steps enabling transition to aggression. Using high-throughput shRNA screening with a validated 3D on-top cellular assay, the study identified COMMD3 as a suppressor of invasive growth in ER+ cells. COMMD3 loss correlated with reduced survival in hormone-dependent and luminal-A-like tumors. Mechanistically, COMMD3 regulated copper signaling via ATP1B1 and copper chelation reduced invasion.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/commd3-loss-drives-invasive-breast-cancer-growth-by-modulating-copper-homeostasis/405555/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/commd3-loss-drives-invasive-breast-cancer-growth-by-modulating-copper-homeostasis/405555.png","ImageObject",300,407,{"name":42,"@type":43},"Hazel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is understanding COMMD3 loss important in breast cancer progression?","Question",{"text":63,"@type":64},"COMMD3 loss was linked to increased invasive behavior and shorter survival, particularly in hormone-dependent and luminal-A-like breast cancers.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study identify COMMD3 as a growth suppressive factor?",{"text":68,"@type":64},"It used high-throughput shRNA screening on a validated 3D on-top cellular assay to find genes that suppress tumor cell growth.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does copper signaling play according to this research?",{"text":72,"@type":64},"RNA sequencing indicated COMMD3 influences copper signaling by regulating ATP1B1, and copper chelation with tetrathiomolybdate reduced invasive growth through apoptosis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},405555,1791492352,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":55,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":107,"preview_page_count":4},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Hancock et al. J Exp Clin Cancer Res (2023) 42:90 [https://doi.org/10.1186/s13046-023-02663-8](https://doi.org/10.1186/s13046-023-02663-8)  \nJournal of Experimental & Clinical Cancer Research  \n RESEARCH Open Access  \nCOMMD3 loss drives invasive breast cancer   growth by modulating copper homeostasis  \nJanelle L. Hancock 1†, Murugan Kalimutho 1†, Jasmin Straube 1, Malcolm Lim2, Irma Gresshoff2, Jodi M. Saunus2,3, Jason S. Lee 1, Sunil R. Lakhani2, Kaylene J. Simpson4,5, Ashley I. Bush6, Robin L. Anderson7,8* and  \nKum Kum Khanna 1*  \nAbstract  \nBackground Despite overall improvement in breast cancer patient outcomes from earlier diagnosis and personalised treatment approaches, some patients continue to experience recurrence and incurable metastases. It is therefore imperative to understand the molecular changes that allow transition from a non-aggressive state to a more aggressive phenotype. This transition is governed by a number offactors.  \nMethods As crosstalk with extracellular matrix (ECM) is critical for tumour cell growth and survival, we applied high throughput shRNA screening on a validated‘3D on-top cellular assay’ to identify novel growth suppressive mechanisms.  \nResults A number of novel candidate genes were identified. We focused on COMMD3, a previously poorly characterised gene that suppressed invasive growth of ER + breast cancer cells in the cellular assay. Analysis of published expression data suggested that COMMD3 is normally expressed in the mammary ducts and lobules, that expression is lost in some tumours and that loss is associated with lower survival probability. We performed immunohistochemical analysis of an independent tumour cohort to investigate relationships between COMMD3 protein expression, phenotypic markers and disease-specific survival. This revealed an association between COMMD3 loss and shorter survival in hormone-dependent breast cancers and in particularly luminal-A-like tumours (ER+/Ki67-low; 10-year survival probability 0.83 vs. 0.73 for COMMD3-positive and-negative cases, respectively) . Expression of COMMD3 in luminal-Alike tumours was directly associated with markers of luminal differentiation: c-KIT, ELF5, androgen receptor and tubule formation (the extent of normal glandular architecture; p \u003C 0. 05) . Consistent with this, depletion of COMMD3 induced invasive spheroid growth in ER + breast cancer cell lines in vitro, while Commd3 depletion in the relatively indolent 4T07 TNBC mouse cell line promoted tumour expansion in syngeneic Balb/c hosts. Notably, RNA sequencing revealed a role for COMMD3 in copper signalling, via regulation of the Na+/K+-ATPase subunit, ATP1B1 . Treatment of COMMD3-depleted cells with the copper chelator, tetrathiomolybdate, significantly reduced invasive spheroid growth via induction of apoptosis.  \nConclusion Overall, we found that COMMD3 loss promoted aggressive behaviour in breast cancer cells. Keywords Breast cancer, Tumour suppressor, 3D screen, COMMD3, Copper signalling  \n†Janelle L. Hancock and Murugan Kalimutho contributed equally to this work.  \n*Correspondence:  \nRobin L. Anderson [Robin.Anderson@onjcri.org.au](Robin.Anderson@onjcri.org.au)[ ](Robin.Anderson@onjcri.org.au)Kum Kum Khanna[kumkum.khanna@qimrberghofer.edu.au](kumkum.khanna@qimrberghofer.edu.au)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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 an","cbCaielc2e2J5FTU","https://ap.wps.com/l/cbCaielc2e2J5FTU","pdf",3704634,16,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Main article background\n## Breast cancer burden and molecular subtypes\n## Need for mechanistic understanding","[{\"question\":\"Why is understanding COMMD3 loss important in breast cancer progression?\",\"answer\":\"COMMD3 loss was linked to increased invasive behavior and shorter survival, particularly in hormone-dependent and luminal-A-like breast cancers.\"},{\"question\":\"How did the study identify COMMD3 as a growth suppressive factor?\",\"answer\":\"It used high-throughput shRNA screening on a validated 3D on-top cellular assay to find genes that suppress tumor cell growth.\"},{\"question\":\"What role does copper signaling play according to this research?\",\"answer\":\"RNA sequencing indicated COMMD3 influences copper signaling by regulating ATP1B1, and copper chelation with tetrathiomolybdate reduced invasive growth through apoptosis.\"}]","COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis | PDF",1790560546]