[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-349537-105":59,"doc-detail-349537-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","foxk1-a-multifaceted-regulator-in-metabolic-reprogramming-and-disease-progression","FOXK1: a multifaceted regulator in metabolic reprogramming and disease progression","","Forkhead box K1 (FOXK1) is a key member of the FOX transcription factor family, acting as a signal-responsive regulator of cellular metabolism, proliferation, differentiation, and stress adaptation. FOXK1 activity is controlled through a multilayered network involving genetic and epigenetic alterations, transcriptional regulation, non-coding RNAs, and post-translational modifications that coordinate FOXK1 stability, localization, and transcriptional activity. Dysregulation can sustain FOXK1 activation and drive disease. In cancer, FOXK1 promotes metabolic reprogramming, cancer stemness, EMT, invasion, metastasis, vasculogenic mimicry, and therapeutic resistance, while accumulating evidence links it to metabolic, inflammatory, reproductive, and neurological disorders. Given its central role, FOXK1 is explored as a therapeutic target through systematic review of its mechanisms and translation challenges.",{"@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/foxk1-a-multifaceted-regulator-in-metabolic-reprogramming-and-disease-progression/349537/",{"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/foxk1-a-multifaceted-regulator-in-metabolic-reprogramming-and-disease-progression/349537.png","ImageObject",300,407,{"name":92,"@type":93},"nayy☆","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-25","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How is FOXK1 activity regulated at the molecular level?","Question",{"text":112,"@type":113},"FOXK1 activity is controlled by genetic and epigenetic alterations, transcriptional regulation, non-coding RNAs, and post-translational modifications that coordinate its stability, localization, and transcriptional output.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What roles does FOXK1 play in cancer progression?",{"text":117,"@type":113},"In cancer, FOXK1 mainly functions as an oncogenic transcription factor promoting metabolic reprogramming, cancer stem cell properties, epithelial-mesenchymal transition, invasion, metastasis, vasculogenic mimicry, and therapeutic resistance.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is FOXK1 considered a potential therapeutic target beyond oncology?",{"text":121,"@type":113},"Emerging evidence associates FOXK1 with metabolic disorders, inflammatory diseases, reproductive dysfunction, and neurological conditions, indicating broader, context-dependent pathological roles that may be targetable.","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},349537,1790296005,{"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":14,"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":36},962090893153,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","He etal. Biology Direct (2026) 21:147 Biology Direct  \n[https://doi.org/10.1186/s13062-026-00862-9](https://doi.org/10.1186/s13062-026-00862-9)  \nREVIEW Open Access  \nFOXK1: a multifaceted regulator in metabolic reprogramming and disease progression  \nTingting He1*, Guangzhi Ma1 and Gang Yuan1*  \nAbstract  \nForkhead box K1 (FOXK1) is an important member of the FOX transcription factor family and functions as a signalresponsive regulator of cellular metabolism, proliferation, differentiation, and stress adaptation. FOXK1 activity is tightly controlled by a multilayered regulatory network, including genetic and epigenetic alterations, transcriptional regulation, non-coding RNAs, and diverse post-translational modifications. These regulatory networks collectively coordinate FOXK1 stability, subcellular localization, and transcriptional activity in a context-dependent manner. Disruption of this tightly balanced regulatory system can lead to sustained FOXK1 activation and contribute to disease pathogenesis. In cancer, FOXK1 predominantly functions as an oncogenic transcription factor that promotes metabolic reprogramming, maintenance of cancer stem cell properties, epithelial-mesenchymal transition, invasion, metastasis, vasculogenic mimicry, and therapeutic resistance. Beyond oncology, emerging evidence further implicates FOXK1 in metabolic disorders, inflammatory diseases, reproductive dysfunction, and neurological conditions, suggesting broader context-dependent pathological functions. Given its central role in multiple disease-associated signaling networks, FOXK1 has emerged as a potential therapeutic target. In this review, we systematically summarize the structural characteristics and regulatory mechanisms of FOXK1, and comprehensively discuss its roles in physiological and pathological processes. We further highlight current advances in FOXK1-targeted therapeutic strategies and address the key challenges for clinical translation. This review provides a conceptual framework for future therapeutic strategies and rational drug development targeting FOXK1 .  \nKeywords FOXK1 activity, Metabolic disorders, Cancer progression, Regulatory mechanism, Context-dependent  \nIntroduction  \nThe FOXK subfamily comprises two closely related members, FOXK1 and FOXK2, which share substantial sequence homology within the forkhead domain and partially overlapping transcriptional properties. Despite this structural similarity, emerging evidence indicates  \n*Correspondence: Tingting He [305795664@qq.com](305795664@qq.com)[ ](305795664@qq.com)Gang Yuan [gangy2021@wchscu.cn](gangy2021@wchscu.cn)  \n1Department of Thoracic Surgery, Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China  \nthat FOXK1 displays more dynamic regulation and stronger disease association, particularly in pathological contexts [1, 2]. Initially identified as a modulator of metabolic pathways and cell cycle progression, FOXK1 has since been recognized as a pivotal player in multiple diseases, particularly cancer, where it integrates complex regulatory networks to drive key oncogenic hallmarks [2–4]. The dysregulation of FOXK1 is driven by multiple mechanisms, including genetic alterations, epigenetic modifications, and ncRNA-mediated regulation, all of which collectively contribute to its aberrant activation in diseases [2]. Unlike other FOX family members that focus on specific biological processes, FOXK1 uniquely regulates three core cancer hallmarks: metabolic  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the lic","cbCair9NgTLrOHhm","https://ap.wps.com/l/cbCair9NgTLrOHhm","pdf",2068183,16,"English","# Abstract\n# Introduction\n## FOXK subfamily overview\n# Regulatory mechanisms overview\n## Genetic and epigenetic alterations\n## Non-coding RNAs\n## Post-translational modifications (PTMs)\n# Structural features of FOXK1\n# FOXK1 in physiology and pathology\n## Cancer-related functions\n## Non-cancer diseases\n# Therapeutic targeting strategies\n## FOXK1-centered approaches\n## Translational challenges","[{\"question\":\"How is FOXK1 activity regulated at the molecular level?\",\"answer\":\"FOXK1 activity is controlled by genetic and epigenetic alterations, transcriptional regulation, non-coding RNAs, and post-translational modifications that coordinate its stability, localization, and transcriptional output.\"},{\"question\":\"What roles does FOXK1 play in cancer progression?\",\"answer\":\"In cancer, FOXK1 mainly functions as an oncogenic transcription factor promoting metabolic reprogramming, cancer stem cell properties, epithelial-mesenchymal transition, invasion, metastasis, vasculogenic mimicry, and therapeutic resistance.\"},{\"question\":\"Why is FOXK1 considered a potential therapeutic target beyond oncology?\",\"answer\":\"Emerging evidence associates FOXK1 with metabolic disorders, inflammatory diseases, reproductive dysfunction, and neurological conditions, indicating broader, context-dependent pathological roles that may be targetable.\"}]","FOXK1: a multifaceted regulator in metabolic reprogramming and disease progression | PDF",1790084244]