[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329331-105":59,"doc-detail-329331-en":122},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":115,"head_meta":117,"extra_data":119,"updated_unix":121},105,"en","breast-cancer-cells-utilize-t3-to-trigger-proliferation-through-cellular-ca-2-modulation","Breast cancer cells utilize T3 to trigger - proliferation through cellular Ca 2+ modulation","","High levels of thyroid hormones are linked to increased risk and advanced stages of breast cancer. Prior work showed that triiodothyronine (T3) enhances mitochondrial ATP production by upregulating Ca2+ handling proteins, increasing mitochondrial Ca2+ uptake and Krebs cycle activity. This study uses live-cell imaging, biochemical assays, and molecular profiling to test whether T3 triggers a Ca2+-driven signaling pathway that boosts proliferation in breast cancer cells. Results show that T3 upregulates IP3R3 via thyroid hormone receptor α, elevating mitochondrial Ca2+ uptake and ATP production while not affecting non-cancerous hTERT-HME1 or PC3 cells.",{"@graph":69,"@context":114},[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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/breast-cancer-cells-utilize-t3-to-trigger-proliferation-through-cellular-ca-2-modulation/329331/",{"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/breast-cancer-cells-utilize-t3-to-trigger-proliferation-through-cellular-ca-2-modulation/329331.png","ImageObject",300,407,{"name":92,"@type":93},"Eden","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"Does the T3 effect apply only to breast cancer cells?","Question",{"text":112,"@type":113},"No. The findings indicate T3 supports proliferation/viability in breast cancer cells but does not affect non-cancerous hTERT-HME1 cells or PC3 prostate carcinoma cells.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},329331,1791082075,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":131,"language":132,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":133,"faqs":134,"seo_title":135,"seo_description":67,"update_tm":136,"read_time":137,"preview_page_count":4},1374391974468,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Tawfik et al.  \nCell Communication and Signaling (2024) 22:533 [https://doi.org/10.1186/s12964-024-01917-y](https://doi.org/10.1186/s12964-024-01917-y)  \nCell Communication and Signaling  \n RESEARCH Open Access  \nBreast cancer cells utilize T3 to trigger  \nproliferation through cellular Ca 2 + modulation  \nInesTawfik1, Katharina Schlick2, Julian Ostaku1, Doruntina Bresilla 1, Sonja Gabrijelčič1, Benjamin Gottschalk1, Alwin Sokolowski3, Ernst Malle1, Katarina Kalinova 1, Martin Hirtl 1 and CorinaT. Madreiter-Sokolowski1,4*  \nAbstract  \nHigh levels of thyroid hormones are linked to increased risk and advanced stages of breast cancer. Our previous work demonstrated that the biologically active triiodothyronine (T3) facilitates mitochondrial ATP production by upregulating Ca2+ handling proteins, thereby boosting mitochondrial Ca2+ uptake and Krebs cycle activity. In this study, different cell types were utilized to investigate whether T3 activates a Ca2+-induced signaling pathway to boost cancer cell proliferation. Using live-cell imaging, biochemical assays, and molecular profiling, differences in intracellular signaling among MCF7 and MDA-MB-468 breast cancer cells, non-cancerous breast cells hTERT-HME1, and PC3 prostate carcinoma cells, previously found to be insensitive to thyroid hormones in terms of proliferation, were investigated. Our findings revealed that T3 upregulates 1,4,5-trisphosphate receptor 3 via thyroid hormone receptor α . This boosts mitochondrial Ca2+ uptake, reduction equivalent yield, and mitochondrial ATP production, supporting the viability and proliferation of breast cancer cells without affecting non-cancerous hTERT-HME1 or PC3 prostate carcinoma cells. Understanding the interplay between T3 signaling, organellar interaction, and breast cancer metabolism could lead to targeted therapies that exploit cancer cell vulnerabilities. Our findings highlight T3 as a crucial regulator of cancer metabolism, reinforcing its potential as a therapeutic target in breast cancer.  \nKeywords Thyroid hormones, Calcium homeostasis, Breast cancer, IP3R3, Mitochondria, Thyroid hormone receptor α  \n*Correspondence:  \nCorinaT. Madreiter-Sokolowski  \n[corina.madreiter@medunigraz.at](corina.madreiter@medunigraz.at)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. 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/.)  \nTawfik etal. Cell Communication and Signaling (2024) 22:533 Page 2 of 18  \nGraphical Abstract  \nIntroduction  \nThe metabolism of cancer cells is marked by dynamic alterations that promote their survival and proliferation [1], presenting a significant challenge in understanding and combating malignancies [2]. In this context, recent studies have shed light on the intricate interplay between cellular signaling pathways and metabolic reprogramming, highlighting the pivotal role of thyroid hormones (THs) as master ","cbCaika00isv8AUc","https://ap.wps.com/l/cbCaika00isv8AUc","pdf",6639248,18,"English","# Abstract\n# Introduction\n## Thyroid hormone regulation and canonical/non-canonical T3 signaling\n## Links between thyroid hormones and cancer risk/stage","[{\"question\":\"Does the T3 effect apply only to breast cancer cells?\",\"answer\":\"No. The findings indicate T3 supports proliferation/viability in breast cancer cells but does not affect non-cancerous hTERT-HME1 cells or PC3 prostate carcinoma cells.\"}]","Breast cancer cells utilize T3 to trigger - proliferation through cellular Ca 2+ modulation | PDF",1789983701,45]