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This study evaluates clinical relevance and links ProT with lung cancer progression, showing high nuclear ProT in early-stage tumors and loss of nuclear ProT in late-stage specimens. Nuclear ProT restricts cell migration, suppresses TGF-β–driven EMT transcriptional programs, and inhibits in vivo metastasis by inducing Smad7 acetylation and TGF-β signaling deregulation.",{"@graph":69,"@context":123},[70,84,106],{"@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/aberrant-expression-of-nuclear-prothymosin-contributes-to-epithelial-mesenchymal-transition-in-lung-cancer/374764/",{"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/aberrant-expression-of-nuclear-prothymosin-contributes-to-epithelial-mesenchymal-transition-in-lung-cancer/374764.png","ImageObject",300,407,{"name":92,"@type":93},"McGucket","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the relationship between nuclear prothymosin α and lung cancer progression?","Question",{"text":113,"@type":114},"High nuclear ProT is observed in early-stage lung cancer, while loss of nuclear ProT appears in late-stage tumor specimens, correlating with progression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does nuclear prothymosin α affect TGF-β–induced epithelial-mesenchymal transition?",{"text":118,"@type":114},"Nuclear ProT suppresses TGF-β–induced EMT by reducing EMT transcription factor expression and inhibiting EMT-associated transcriptional programs.",{"name":120,"@type":111,"acceptedAnswer":121},"What molecular mechanism links ProT to TGF-β signaling regulation?",{"text":122,"@type":114},"ProT triggers Smad7 acetylation-dependent deregulation of TGF-β signaling, enhancing Smad7 stability and competing with Smad2 binding at EMT-related promoters.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},374764,1790243044,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"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":31},1236954412713,"https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Aberrant expression of nuclear prothymosin α contributes to epithelial-mesenchymal transition in lung cancer  \nLiyun Chen 1,2, Chung-Teng Wang3,4, Jia-Ming Chang5,6, Ai-Li Shiau3,4, Gia-Shing Shieh 1,7  \n,  \nYau-Lin Tseng8, Yi-Ting Yen8, Tang-Hsiu Huang9, Li-Hsin Cheng 10, Yu-Chih Wu 11,12, Chao-Liang Wu 1,4,6, Bing-Hua Su 11,12  and Pensee Wu 13  \n1 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n2 Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, USA  \n3 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n4 Tong Yuan Diabetes Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n5 Thoracic Division, Department of Surgery, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan  \n6 Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan  \n7 Department of Urology, Tainan Hospital, Ministry of Health and Welfare, Taiwan  \n8 Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n9 Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n10 Core Laboratory of Organoids Technology, Office of R&D, Taipei Medical University, Taiwan  \n11 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taiwan  \n12 TMU Research Center of Thoracic Medicine, Taipei Medical University, Taiwan  \n13 Keele Medical School, Keele University, UK  \nKeywords  \nepithelial–mesenchymal transition; lung cancer; prothymosin α; Smad7 acetylation; TGF-β  \nCorrespondence  \nB.-H. Su, School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, Taiwan  \nE-mail: [prothymosina@tmu.edu.tw](prothymosina@tmu.edu.tw)  \n[Liyun Chen](Liyun Chen), [Chung-Teng Wang and](Chung-Teng Wang and)[ ](Chung-Teng Wang and)[Jia-Ming Chang contributed equally to this](Jia-Ming Chang contributed equally to this)[ ](Jia-Ming Chang contributed equally to this)[article.](article.)  \n(Received 13 June 2024, revised 22  \nDecember 2024, accepted 31 March 2025, available online 22 April 2025)  \nElevated expression of prothymosin α (ProT) is frequently observed in cancers, but the underlying molecular mechanism remains poorly understood. Here, we report the clinical relevance of ProT expression and its correlation with lung cancer progression. We have shown that ProT was highly expressed in early-stage lung cancer, exhibiting nuclear localization; on the contrary, a loss of nuclear ProT expression was detected in late-stage tumor specimens. Furthermore, the expression of nuclear ProT impaired lung cancer cell migration, suppressed TGF-β-induced epithelial-tomesenchymal transition (EMT)-associated transcription factor expression, and inhibited in vivo tumor metastasis. The suppressive effect of ProT was further found to trigger Smad7 acetylation-dependent deregulation of TGF-β signaling. ProT enhanced Smad7 stability by promoting its lysine acetylation, thereby competing with the binding of Smad2 to the SNAI1, TWIST1, and ZEB1 promoters. Eventually, the binding of Smad7 in the presence of ProT resulted in reduced expression of the EMT transcription factors, leading to the inhibition of TGF-β-induced EMT and tumor  \nAbbreviations  \nCBP, CREB-binding protein; ChIP, chromatin immunoprecipitation; DMFS, distant metastasis-free survival; EMT, epithelial-to-mesenchymal transition; FBS, fetal bovine serum; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; IHC, immunohistochemistry; IP, immunoprecipitation; Luc, luciferase; MMPs, matrix metalloproteinases; NLS, nuclear localization signal; OS, overall survival; PBS, phosphate-buffered saline; PFS, progression-free ","cbCaiqEKFTmru65F","https://ap.wps.com/l/cbCaiqEKFTmru65F","pdf",5101530,"English","# Keywords and correspondence\n# Clinical relevance of ProT in lung cancer\n## ProT expression patterns across tumor stages\n## Functional effects on EMT and metastasis\n# Mechanistic link via Smad7 acetylation\n# Introduction","[{\"question\":\"What is the relationship between nuclear prothymosin α and lung cancer progression?\",\"answer\":\"High nuclear ProT is observed in early-stage lung cancer, while loss of nuclear ProT appears in late-stage tumor specimens, correlating with progression.\"},{\"question\":\"How does nuclear prothymosin α affect TGF-β–induced epithelial-mesenchymal transition?\",\"answer\":\"Nuclear ProT suppresses TGF-β–induced EMT by reducing EMT transcription factor expression and inhibiting EMT-associated transcriptional programs.\"},{\"question\":\"What molecular mechanism links ProT to TGF-β signaling regulation?\",\"answer\":\"ProT triggers Smad7 acetylation-dependent deregulation of TGF-β signaling, enhancing Smad7 stability and competing with Smad2 binding at EMT-related promoters.\"}]","Aberrant expression of nuclear prothymosin α contributes to epithelial-mesenchymal transition in lung cancer | PDF",1790202352]