[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332572-105":59,"doc-detail-332572-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","iron-fe3-dependent-reactivation-of-telomerase-drives-colorectal-cancers-research-article","Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers - Research Article","","Iron-rich red meat consumption and hereditary iron overload increase colorectal cancer risk, yet the metal-mediated signaling mechanism behind oncogenesis has been unclear. Using fresh colorectal cancer samples, the study identifies Pirin as an iron sensor that reactivates dormant telomerase by restoring the hTERT subunit in an iron-(Fe3+)-dependent manner. Chemical genetic screening plus isothermal dose-response fingerprinting and mass spectrometry find SP2509, which inhibits Pirin-mediated hTERT reactivation by competing for (Fe3+) binding. The work links iron biology with telomerase activation and supports telomerase reactivation as a druggable driver pathway.",{"@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":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/iron-fe3-dependent-reactivation-of-telomerase-drives-colorectal-cancers-research-article/332572/",{"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/iron-fe3-dependent-reactivation-of-telomerase-drives-colorectal-cancers-research-article/332572.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does the study connect iron to colorectal cancer development?","Question",{"text":112,"@type":113},"It identifies Pirin as an iron sensor that reactivates dormant telomerase by restoring iron-(Fe3+)-dependent hTERT activity, driving colorectal cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is SP2509 and what does it do?",{"text":117,"@type":113},"SP2509 is a small molecule that specifically inhibits Pirin-mediated hTERT reactivation in colorectal cancers by competing with iron-(Fe3+) binding.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is telomerase reactivation central to the proposed mechanism?",{"text":121,"@type":113},"Telomerase activity is required to elongate critically short telomeres in cancer cells, and the study focuses on transcriptional reactivation of the hTERT subunit of telomerase.","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},332572,1790196931,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":26,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","ReseaRch aRticle  \nIron-(Fe 3 + )-Dependent Reactivation of Telomerase Drives Colorectal Cancers   \nRaghuvaran Shanmugam 1, Prativa Majee 1, Wei Shi 1, Mert B. Ozturk 1, Thamil S. Vaiyapuri 1, Khaireen Idzham1, Anandhkumar Raju1, Seung H. Shin1, Kerem Fidan1, Joo-Leng Low2, Joelle Y.H. Chua1, Yap C. Kong2, Ong Y. Qi1, Emile Tan3, Aik Y. Chok3, Isaac Seow-En3, Ian Wee3, Dominique C. Macalinao4, Dawn Q. Chong4, Hong Y. Chang5, Fiona Lee2, Wei Q. Leow3, Maki Murata-Hori2, Zhang Xiaoqian2, Chia Shumei2, Chris S.H. Tan6, Ramanuj Dasgupta2, Iain B. Tan2,4,7, and Vinay Tergaonkar1,8  \nOver-consumption of iron-rich red meat and hereditary or genetic iron overload are  \nassociated with an increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by reactivating the dormant human telomerase reverse transcriptase (hTERT) subunit of the telomerase holoenzyme in an iron-(Fe3+)-dependent manner and thereby drives colorectal cancers. Chemical genetic screens combined with isothermal dose-response fingerprinting and mass spectrometry identified a small molecule SP2509 that specifically inhibits Pirin-mediated hTERT reactivation in colorectal cancers by competing with iron-(Fe3+) binding. Our findings, first to document how metal ions reactivate telomerase, provide a molecular mechanism for the well-known association between red meat and increased incidence of colorectal cancers. Small molecules like SP2509 represent a novel modality to target telomerase that acts as a driver of 90% of human cancers and is yet to be targeted in clinic.  \nSIgnIFICanCe: We show how iron-(Fe3+) in collusion with genetic factors reactivates telomerase, providing a molecular mechanism for the association between iron overload and increased incidence of colorectal cancers. Although no enzymatic inhibitors of telomerase have entered the clinic, we identify SP2509, a small molecule that targets telomerase reactivation and function in colorectal cancers.  \nintRoduction  \nGenetic and nongenetic factors contribute to the etiology (1) of colorectal cancers, the third most common cancer worldwide (2) . Population-based studies have documented an increased incidence of colorectal cancers with enhanced consumption of red meat (3, 4) . Heterocyclic amines, polycyclic aromatic hydrocarbons, and alkylating agents, such as N-nitroso-compounds and diazoacetate, present in red meat are potential carcinogens and have been suggested to be the causative agents linking red meat to increased colorectal cancer risk (5–7) . Similarly, meta-analysis has shown an increased incidence of colorectal cancer with higher dietary iron intake (8). Mutations leading to hereditary hemochromatosis, which causes abnormally high iron accumulation, are linked to significantly higher rates of colorectal cancers (9–12) . However, these studies have not answered ifor how high iron levels may drive colorectal cancer development. Although iron is indispensable for normal cellular activity, abnormal levels can cause tissue damage through free radical production and DNA damage (13) . An enhancement in cancer cell  \n1Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore. 2Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore. 3Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore. 4Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.  \n5Experimental Drug Development Center, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore. 6Department of Chemistry, College of Science, Southern University of Science and Techno","cbCaigzp2TpBCwNW","https://ap.wps.com/l/cbCaigzp2TpBCwNW","pdf",13666418,24,"English","# Introduction\n## Red meat, dietary iron, and colorectal cancer risk\n## Mechanistic context: iron, cellular damage, and oncogenic signaling\n## Telomerase and hTERT transcriptional reactivation","[{\"question\":\"How does the study connect iron to colorectal cancer development?\",\"answer\":\"It identifies Pirin as an iron sensor that reactivates dormant telomerase by restoring iron-(Fe3+)-dependent hTERT activity, driving colorectal cancers.\"},{\"question\":\"What is SP2509 and what does it do?\",\"answer\":\"SP2509 is a small molecule that specifically inhibits Pirin-mediated hTERT reactivation in colorectal cancers by competing with iron-(Fe3+) binding.\"},{\"question\":\"Why is telomerase reactivation central to the proposed mechanism?\",\"answer\":\"Telomerase activity is required to elongate critically short telomeres in cancer cells, and the study focuses on transcriptional reactivation of the hTERT subunit of telomerase.\"}]","Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers - Research Article | PDF",1789998766]