[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-329218-105":3,"doc-detail-329218-en":81,"detail-sidebar-cat-0-en-105":99},{"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","decoding-cancer-through-silencing-the-mitochondrial-gatekeeper-vdac1","Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1","","Mitochondria coordinate metabolism, apoptosis, cell-cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) acts as a mitochondrial gatekeeper controlling ion, Ca2+, nucleotide, and metabolite flux and contributes to mitochondria-mediated apoptosis. Many cancers show metabolic reprogramming, including the Warburg effect, and VDAC1 is often overexpressed. Silencing VDAC1 with specific siRNA rewires malignant metabolism, reduces tumor growth, invasiveness, and stemness, and suppresses EMT.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/decoding-cancer-through-silencing-the-mitochondrial-gatekeeper-vdac1/329218/",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/decoding-cancer-through-silencing-the-mitochondrial-gatekeeper-vdac1/329218.png","ImageObject",300,407,{"name":42,"@type":43},"Skyler","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does VDAC1 play in mitochondria and cancer biology?","Question",{"text":63,"@type":64},"VDAC1 functions as a mitochondrial gatekeeper controlling ion and metabolite transport and contributes to mitochondria-mediated apoptosis. It also sits at the interface of mitochondrial and cellular energy regulation, making it relevant to cancer cell survival.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does silencing VDAC1 affect cancer phenotypes?",{"text":68,"@type":64},"Silencing VDAC1 using specific siRNA induces metabolic rewiring and reverses oncogenic properties, including reduced tumor growth, invasiveness, and stemness, along with suppression of epithelial–mesenchymal transition.",{"name":70,"@type":61,"acceptedAnswer":71},"Does VDAC1 depletion influence the tumor microenvironment and gene regulation?",{"text":72,"@type":64},"Yes. VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and changing expression of extracellular matrix- and structure-related genes, including collagens and glycoproteins.","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},329218,1790073667,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98},2336464648746,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c",7,"biomolecules  \nReview  \nDecoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1  \nTasleem Arif 1,2, *, Anna Shteinfer-Kuzmine 3 and Varda Shoshan-Barmatz 3,4, *  \nCitation: Arif, T.; Shteinfer-Kuzmine, A.; Shoshan-Barmatz, V. Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1 . Biomolecules 2024, 14, 1304 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom14101304  \nAcademic Editor: Ladislav Andˇera  \nReceived: 26 August 2024  \nRevised: 13 October 2024  \nAccepted: 14 October 2024  \nPublished: 15 October 2024  \nCopyright: © 2024 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA  \n2 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA  \n3 National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; [shteinfe@post.bgu.ac.il](shteinfe@post.bgu.ac.il)  \n4 Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel  \n* Correspondence: [txa764@miami.edu](txa764@miami.edu) (T.A.); [vardasb@ngu.ac.il](vardasb@ngu.ac.il) (V.S.-B.)  \nAbstract: Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca2+, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca2+ homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health. Most cancer cells undergo metabolic reprogramming, often referred to as the “Warburg effect”, supplying tumors with energy and precursors for the biosynthesis of nucleic acids, phospholipids, fatty acids, cholesterol, and porphyrins. Given its multifunctional nature and overexpression in many cancers, VDAC1 presentsan attractive target for therapeutic intervention. Our research has demonstrated that silencing VDAC1 expression using specific siRNA in various tumor types leads to a metabolic rewiring of the malignant cancer phenotype. This results in a reversal of oncogenic properties that include reduced tumor growth, invasiveness, stemness, epithelial–mesenchymal transition. Additionally, VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and modifying the expression of extracellular matrix-and structure-related genes, such as collagens and glycoproteins. Furthermore, VDAC1 depletion affects several epigenetic-related enzymes and substrates, includingthe acetylation-related enzymes SIRT1, SIRT6, and HDAC2, which in turn modify the acetylation and methylation profiles of histone 3 and histone 4 . These epigenetic changes can explain the altered expression levels of approximately 4000 genes that are associated with reversing cancer cells oncogenic properties. Given VDAC1’s critical role in regulating metabolic and energy processes, targeting it offers a promising strategy for anti-cancer therapy. We also highlight the role of VDAC1 expression in various disease pathologies, including cardiovascular, neurodegenerative, and viral and bacterial infections, as explored through siRNA targeting VDAC1 . Thus, this review underscores the potential of targeting VDAC1 as a strategy for addressing high-energy-demand cancers. By thoroughly understandi","cbCainieiHpuxqr1","https://ap.wps.com/l/cbCainieiHpuxqr1","pdf",3541274,27,"English","# Overview\n# VDAC1 Structure and Multifunctional Role\n## VDAC1 targeting in cancer therapy","[{\"question\":\"What role does VDAC1 play in mitochondria and cancer biology?\",\"answer\":\"VDAC1 functions as a mitochondrial gatekeeper controlling ion and metabolite transport and contributes to mitochondria-mediated apoptosis. It also sits at the interface of mitochondrial and cellular energy regulation, making it relevant to cancer cell survival.\"},{\"question\":\"How does silencing VDAC1 affect cancer phenotypes?\",\"answer\":\"Silencing VDAC1 using specific siRNA induces metabolic rewiring and reverses oncogenic properties, including reduced tumor growth, invasiveness, and stemness, along with suppression of epithelial–mesenchymal transition.\"},{\"question\":\"Does VDAC1 depletion influence the tumor microenvironment and gene regulation?\",\"answer\":\"Yes. VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and changing expression of extracellular matrix- and structure-related genes, including collagens and glycoproteins.\"}]","Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1 | PDF",1789983128,68,{"code":4,"msg":82,"data":100},[101,105,109,113,118,123,126,131,136,139,143],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},5,"Comic",60,"comic",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},6,"Technology",50,"technology",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":124,"slug":125},40,"healthcare",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":129,"slug":130},8,"Research & Report",30,"research-report",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":134,"slug":135},9,"Religion & Spirituality",20,"religion-spirituality",{"id":134,"doc_module":4,"doc_module_name":25,"category_name":137,"show_sort_weight":134,"slug":138},"World Cup","world-cup",{"id":140,"doc_module":4,"doc_module_name":25,"category_name":141,"show_sort_weight":140,"slug":142},10,"Lifestyle","lifestyle",{"id":144,"doc_module":4,"doc_module_name":25,"category_name":145,"show_sort_weight":114,"slug":146},19,"General","general"]