{"id":29865,"date":"2022-07-22T16:05:43","date_gmt":"2022-07-22T08:05:43","guid":{"rendered":"https:\/\/www.csi.nus.edu.sg\/web\/?p=29865"},"modified":"2023-04-03T10:53:05","modified_gmt":"2023-04-03T02:53:05","slug":"identification-of-mechanism-of-cancer-cell-specific-reactivation-of-htert-offers-therapeutic-opportunities-for-blocking-telomerase-specifically-in-human-colorectal-cancer-nucleic-acids-res-june-202","status":"publish","type":"post","link":"https:\/\/csi.nus.edu.sg\/identification-of-mechanism-of-cancer-cell-specific-reactivation-of-htert-offers-therapeutic-opportunities-for-blocking-telomerase-specifically-in-human-colorectal-cancer-nucleic-acids-res-june-202\/","title":{"rendered":"Identification of Mechanism of Cancer-cell-specific Reactivation of hTERT Offers Therapeutic Opportunities for Blocking Telomerase Specifically in Human Colorectal Cancer (Nucleic Acids Res., June 2022)"},"content":{"rendered":"<p><span class=\"authors-list-item \">Semih Can Ak?nc?lar<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Joelle Yi Heng Chua<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Qin Feng Ng<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Claire Hian Tzer Chan<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Zahra Eslami-S<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Kaijing Chen<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Joo-Leng Low<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>3<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Surendar Arumugam<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Luay Aswad<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Clarinda Chua<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>4<span class=\"author-sup-separator\">\u00a0<\/span>5<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Iain Beehuat Tan<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>4<span class=\"author-sup-separator\">\u00a0<\/span>5<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Ramanuj DasGupta<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>3<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Melissa Jane Fullwood<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<span class=\"author-sup-separator\">\u00a0<\/span>6<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Vinay Tergaonkar<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<span class=\"author-sup-separator\">\u00a0<\/span>7<span class=\"author-sup-separator\">\u00a0<\/span>8<\/sup><\/span><\/p>\n<h3 class=\"title\">Affiliations<\/h3>\n<ul class=\"item-list\">\n<li data-affiliation-id=\"affiliation-1\"><sup class=\"key\">1<\/sup>Division of Cancer Genetics and Therapeutics, Laboratory of NF?B Signaling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 138673, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-2\"><sup class=\"key\">2<\/sup>Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-3\"><sup class=\"key\">3<\/sup>Laboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, 138672, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-4\"><sup class=\"key\">4<\/sup>Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 138672, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-5\"><sup class=\"key\">5<\/sup>Department of Medical Oncology, National Cancer Centre Singapore, 169610, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-6\"><sup class=\"key\">6<\/sup>School of Biological Sciences, Nanyang Technological University, 637551, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-7\"><sup class=\"key\">7<\/sup>Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 119074, Singapore.<\/li>\n<li data-affiliation-id=\"affiliation-8\"><sup class=\"key\">8<\/sup>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 117596, Singapore.<\/li>\n<\/ul>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"enc-abstract\" class=\"abstract-content selected\">\n<p>Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter present in 19% of cancers are recognized as key drivers of hTERT reactivation, mechanisms by which wildtype hTERT (WT-hTERT) promoter is reactivated, in majority of human cancers, remain unknown. Using primary colorectal cancers (CRC) we identified Tert INTeracting region 2 (T-INT2), the critical chromatin region essential for reactivating WT-hTERT promoter in CRCs. Elevated ?-catenin and JunD level in CRC facilitates chromatin interaction between hTERT promoter and T-INT2 that is necessary to turn on hTERTexpression. Pharmacological screens uncovered salinomycin, which inhibits JunD mediated hTERT-T-INT2 interaction that is required for the formation of a stable transcription complex on the hTERT promoter. Our results showed for the first time how known CRC alterations, such as APC, lead to WT-hTERT promoter reactivation during stepwise-tumorigenesis and provide a new perspective for developing cancer-specific drugs.<\/p>\n<\/div>\n<p><span class=\"identifier pubmed\"><span class=\"id-label\">PMID:\u00a0<\/span><strong class=\"current-id\" title=\"PubMed ID\">35697349\u00a0 <\/strong><\/span>DOI:\u00a0<a class=\"id-link\" href=\"https:\/\/doi.org\/10.1093\/nar\/gkac479\" target=\"_blank\" rel=\"noopener noreferrer\" data-ga-category=\"full_text\" data-ga-action=\"DOI\">10.1093\/nar\/gkac479<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter present in 19% of cancers are recognized as key drivers of hTERT reactivation, mechanisms by which wildtype hTERT (WT-hTERT) promoter is reactivated, in majority of human cancers, remain unknown. <\/p>\n","protected":false},"author":1,"featured_media":32641,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"","footnotes":""},"categories":[15,16,23],"tags":[],"class_list":["post-29865","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-15","category-latest-happenings","category-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Identification of Mechanism of Cancer-cell-specific Reactivation of hTERT Offers Therapeutic Opportunities for Blocking Telomerase Specifically in Human Colorectal Cancer (Nucleic Acids Res., June 2022) - NUS CSI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"http:\/\/csi.nus.edu.sg\/identification-of-mechanism-of-cancer-cell-specific-reactivation-of-htert-offers-therapeutic-opportunities-for-blocking-telomerase-specifically-in-human-colorectal-cancer-nucleic-acids-res-june-202\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Identification of Mechanism of Cancer-cell-specific Reactivation of hTERT Offers Therapeutic Opportunities for Blocking Telomerase Specifically in Human Colorectal Cancer (Nucleic Acids Res., June 2022) - NUS CSI\" \/>\n<meta property=\"og:description\" content=\"Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. 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