[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332781-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332781-en":131},{"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","combatting-cellular-immortality-in-cancers-by-targeting-the-shelterin-protein-complex","Combatting cellular immortality in cancers by targeting the shelterin protein complex","","Shelterin proteins (TERF1, TERF2, TPP1, TINF2, POT1) safeguard telomeres, suppress improper repair signaling, and govern telomerase activity; alterations can drive cancer progression. An in-silico study assesses shelterin across tumour samples from multiple cancers using mutation plots, phylogenetic trees, and sequence alignments. Network pharmacology identifies TERF1 as essential and highlights RUNX1, CTCF, and KDM2B as candidate biomarkers via interactions with miRNAs and shelterin proteins. MCODE analysis reveals ncRNA subnetworks, and shelterin expression correlates with patient survival in 24 cancer types. Spearman/Pearson tests link TERF1 levels across cancers, and TPP1-associated glycans illuminate glycosylated sites relevant to tumorigenesis. Results provide molecular signatures supporting shelterin targeting for anti-cancer therapies and prognostic prediction.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/combatting-cellular-immortality-in-cancers-by-targeting-the-shelterin-protein-complex/332781/",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/combatting-cellular-immortality-in-cancers-by-targeting-the-shelterin-protein-complex/332781.png","ImageObject",300,407,{"name":42,"@type":43},"Quinn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role do shelterin proteins play in telomere maintenance and cancer?","Question",{"text":63,"@type":64},"Shelterin proteins protect telomeres, prevent inappropriate repair activation, and regulate telomerase activity. Changes in shelterin can facilitate cancer progression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the study performed to evaluate shelterin across cancers?",{"text":68,"@type":64},"The research uses an in-silico workflow including mutation plots, phylogenetic trees, sequence alignments, and network pharmacology. MCODE analysis identifies subnetworks of ncRNAs interacting with shelterin proteins.",{"name":70,"@type":61,"acceptedAnswer":71},"Which shelterin protein and biomarkers were highlighted by network pharmacology?",{"text":72,"@type":64},"Network pharmacology identifies TERF1 as an essential shelterin protein. Transcription factors RUNX1, CTCF, and KDM2B are proposed as potential biomarkers based on interactions with miRNAs and shelterin proteins.","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},332781,1790555725,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"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":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":118,"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":104,"preview_page_count":4},962075114765,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Chakraborty and Banerjee Biology Direct (2024) 19:120  \n[https://doi.org/10.1186/s13062-024-00552-4](https://doi.org/10.1186/s13062-024-00552-4)  \nBiology Direct  \n RESEARCH Open Access  \nCombatting cellular immortality in cancers by targeting the shelterin protein complex  \nSohini Chakraborty1 and Satarupa Banerjee 1*  \nAbstract  \nShelterin proteins (TERF1, TERF2, TPP1, TINF2, POT1) protect telomeres, prevent unwarranted repair activation, and regulate telomerase activity. Alterations in these proteins can lead to cancer progression. This study uses an in-silico approach to examine shelterin in tumour samples across various cancers, employing mutation plots, phylogenetic trees, and sequence alignments. Network pharmacology identified TERF1 as an essential shelterin protein and transcription factors RUNX1, CTCF, and KDM2B as potential biomarkers due to their interactions with miRNAs and shelterin proteins. We performed MCODE analysis to identify subnetworks of ncRNAs interacting with the shelterin proteins. Shelterin expression predicted patient survival in 24 cancer types, with TERF1, TERF2, TINF2, and POT1 significantly expressed in testicular, AML, prostate, breast and renal cancers, respectively, and TPP1 in AML and skin cancer. Spearman and Pearson’s analyses showed significant correlations ofTERF1 across cancers, with near-significant correlations for all five proteins in different cancer datasets like breast cancer, kidney renal papillary and lung squamous cell carcinoma, skin cutaneous melanoma, etc.,. Shelterin expression correlated with patient survival in breast, renal, lung, skin, uterine, and gastric cancers. Insights into TPP1-associated glycans highlighted glycosylated sites contributing to tumorigenesis. This study provides molecular signatures for further functional and therapeutic research on shelterin, highlighting its potential as a target for anti-cancer therapies and promising prospects for cancer prognosis and prediction.  \nKeywords Shelterin proteins, RNAs, Network pharmacology, Expression, Patient survival, Correlation  \nIntroduction  \nCells that undergo malignant transformation face the challenge of evading replicative senescence and eventual cell death due to progressive telomere shortening that occurs with each cell division. Telomeres are protected by a specialized protein complex called shelterin or the telosome. This complex comprises proteins TERF1, TERF2, TPP1, POT1 and TINF2, which work together to prevent telomere degradation or fusion. Shelterin plays a critical role in facilitating the formation of T-loop structures, recruiting telomerase, and protecting  \n*Correspondence:  \nSatarupa Banerjee [satarupa.banerjee@vit.ac.in](satarupa.banerjee@vit.ac.in)  \n1 Department of Biotechnology, School of Bioscience and Technology, Vellore Institute of Technology, Vellore 632014, India  \ntelomeres [1]. Moreover, the molecular components of telomerase act as additional factors that influence telomeres’ replicative and protective functions. Often, these components work together with shelterin or other core telomere-binding proteins to orchestrate the intricate events that govern telomere maintenance and stability. When telomere protection is lost, it can lead to chromosome end-to-end fusions and a state of telomere crisis, characterized by extensive genome instability, chromothripsis, kataegis, and tetraploidization, all of which can promote cancer progression. Beyond its role in endprotection, shelterin also functions as a mechanism for sensing telomere length and regulates telomerase activity at the telomere. TERF1 and TERF2 are homodimers that bind to telomeric double-stranded DNA, while the POT1–TPP1 heterodimer binds and caps the telomeric 3′ tail. TINF2 connects the TERF1 and TERF2 dimers  \n© The Author(s) 2024. 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 fo","cbCaip5Z9oFRmmku","https://ap.wps.com/l/cbCaip5Z9oFRmmku","pdf",3656019,"English","# Introduction\n## Shelterin and telomere protection in cancer\n# Abstract\n## Study approach and computational analyses\n## Biomarkers, networks, and survival associations","[{\"question\":\"What role do shelterin proteins play in telomere maintenance and cancer?\",\"answer\":\"Shelterin proteins protect telomeres, prevent inappropriate repair activation, and regulate telomerase activity. Changes in shelterin can facilitate cancer progression.\"},{\"question\":\"How was the study performed to evaluate shelterin across cancers?\",\"answer\":\"The research uses an in-silico workflow including mutation plots, phylogenetic trees, sequence alignments, and network pharmacology. MCODE analysis identifies subnetworks of ncRNAs interacting with shelterin proteins.\"},{\"question\":\"Which shelterin protein and biomarkers were highlighted by network pharmacology?\",\"answer\":\"Network pharmacology identifies TERF1 as an essential shelterin protein. Transcription factors RUNX1, CTCF, and KDM2B are proposed as potential biomarkers based on interactions with miRNAs and shelterin proteins.\"}]","Combatting cellular immortality in cancers by targeting the shelterin protein complex | PDF",1789999494]