[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-374738-105":59,"doc-detail-374738-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","drug-repurposing-screen-identifies-thiostrepton-as-a-novel-regulator-of-the-tumor-suppressor-dab2ip","Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP","","The tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor, controls signal transduction and normally limits multiple oncogenic pathways. Loss of DAB2IP promotes metastasis and drives chemo- and radioresistance, while direct genomic mutation is uncommon and downregulation or inactivation occurs through other mechanisms. To find drugs that raise DAB2IP protein levels, the study performed a drug screen and used CRISPR/Cas9 with HiBiT-tagged prostate cancer models. Thiostrepton increased DAB2IP levels and its anti-cancer effect diminished without DAB2IP, supporting DAB2IP upregulation as a key mediator of thiostrepton activity and a promising therapeutic target.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/drug-repurposing-screen-identifies-thiostrepton-as-a-novel-regulator-of-the-tumor-suppressor-dab2ip/374738/",{"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/drug-repurposing-screen-identifies-thiostrepton-as-a-novel-regulator-of-the-tumor-suppressor-dab2ip/374738.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is DAB2IP considered a promising target in cancer therapy?","Question",{"text":112,"@type":113},"DAB2IP negatively regulates multiple oncogenic pathways, and its loss enhances metastasis and chemo- and radioresistance. Restoring or increasing DAB2IP protein levels reverses aggressive behavior in multiple models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study measure DAB2IP protein levels in cells?",{"text":117,"@type":113},"The researchers used CRISPR/Cas9 to create prostate cancer cell models in which endogenous DAB2IP is fused to HiBiT, enabling sensitive, luminescence-based quantification of protein levels.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does thiostrepton play in relation to DAB2IP?",{"text":121,"@type":113},"Thiostrepton increased DAB2IP protein levels in the screening and its cancer-inhibitory effect was reduced when DAB2IP was absent. This indicates that upregulation of DAB2IP contributes to thiostrepton’s anti-tumoral activity.","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},374738,1790270190,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"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":145},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Article  \nDrug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP  \nRossella De Florian Fania 1, *,†, Serena Maiocchi 1,2,‡, Raffaella Klima 2, Monica Rossin 1, Valeria Pellegrini 1,§, Sabrina Ghetti 3,∥, Davide Selvestrel 2, Maria Chiara Mattevi 4, Luca L. Fava 3, Luca Braga 2,¶  \nand Licio Collavin 1, *,¶  \nAcademic Editor: Ruey-Bing Yang  \nReceived: 4 June 2025  \nRevised: 30 July 2025  \nAccepted: 6 August 2025  \nPublished: 8 August 2025  \nCitation: De Florian Fania, R.; Maiocchi, S.; Klima, R.; Rossin, M.; Pellegrini, V.; Ghetti, S.; Selvestrel, D.; Mattevi, M.C.; Fava, L.L.; Braga, L.; et al. Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP. Biomolecules 2025, 15, 1147 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom15081147  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Life Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy  \n2 International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy  \n3 Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo, Italy  \n4 Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Via Gallini 2, 33081 Aviano, Italy  \n* [Correspondence: rdeflor1@jhmi.edu](Correspondence: rdeflor1@jhmi.edu) (R.D.F.F.); lcollavin@units.it (L.C.)  \n† Current address: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.  \n‡ Current address: International School for Advanced Studies (SISSA), Via Bonomea, 265, 34136 Trieste, Italy.  \n§ Current address: IRCCS MultiMedica, PST, Via Fantoli 16/15, 20138 Milan, Italy.  \n∥ Current address: Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.  \n¶ These authors contributed equally to this work.  \nAbstract  \nThe tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor protein, modulates signal transduction in response to several extracellular stimuli, negatively regulating multiple oncogenic pathways. Accordingly, the loss of DAB2IP in tumor cells fosters metastasis and enhances chemo-and radioresistance. DAB2IP is rarely mutated in cancer but is frequently downregulated or inactivated by multiple mechanisms. Solid experimental evidence shows that DAB2IP reactivation reduces cancer aggressiveness in tumors driven by multiple different oncogenic mutations, making this protein an interesting target for cancer therapy. Considering this evidence, we screened a drug library to identify molecules that increase DAB2IP protein levels. We employed CRISPR/Cas9 gene editing to generate two prostate cancer cell models in which endogenous DAB2IP is fused to HiBiT, a peptide tag that enables luminescence-based detection of protein levels in a sensitive and quantitative manner. Using this approach, we identified drugs able to increase DAB2IP levels. We focused our attention on thiostrepton, a natural cyclic oligopeptide antibiotic that has been reported to inhibit the survival of various cancer cell lines. Functional experiments revealed that the cancer-inhibitory effect of thiostrepton is reduced in the absence of DAB2IP, suggesting that upregulation of this protein contributes to its action. These findings encourage further development of thiostrepton for the treatment of solid cancers and unveil a novel molecular target underlying its anti-tumoral activity.  \nKeywords: high-throughput screeni","cbCaikDuomFpU0xI","https://ap.wps.com/l/cbCaikDuomFpU0xI","pdf",31172088,18,"English","# Introduction\n## DAB2IP function and therapeutic rationale\n## Drug resistance and need for new strategies","[{\"question\":\"Why is DAB2IP considered a promising target in cancer therapy?\",\"answer\":\"DAB2IP negatively regulates multiple oncogenic pathways, and its loss enhances metastasis and chemo- and radioresistance. Restoring or increasing DAB2IP protein levels reverses aggressive behavior in multiple models.\"},{\"question\":\"How did the study measure DAB2IP protein levels in cells?\",\"answer\":\"The researchers used CRISPR/Cas9 to create prostate cancer cell models in which endogenous DAB2IP is fused to HiBiT, enabling sensitive, luminescence-based quantification of protein levels.\"},{\"question\":\"What role does thiostrepton play in relation to DAB2IP?\",\"answer\":\"Thiostrepton increased DAB2IP protein levels in the screening and its cancer-inhibitory effect was reduced when DAB2IP was absent. This indicates that upregulation of DAB2IP contributes to thiostrepton’s anti-tumoral activity.\"}]","Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP | PDF",1790202294,45]