[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-405733-105":59,"doc-detail-405733-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","uncovering-tumor-promoting-roles-of-activin-a-in-pancreatic-ductal-adenocarcinoma","Uncovering Tumor-Promoting Roles of Activin A in Pancreatic Ductal Adenocarcinoma","","Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with frequent metastasis and cachexia, and elevated circulating activin A predicts poor patient survival. The study demonstrates abundant activin A in tumor and stromal cells in PDAC tissue microarrays and mouse sections. Tumor-targeted Inhba siRNA delivery suppresses activin A, retarding growth, metastasis, and cachexia and improving survival compared with control. Mechanistically, activin A suppression reduces Ki67 while increasing α-SMAhigh fibroblasts and cytotoxic T cells, and in vitro activin A drives KPC proliferation via a SMAD3-dependent PSC response.",{"@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/uncovering-tumor-promoting-roles-of-activin-a-in-pancreatic-ductal-adenocarcinoma/405733/",{"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/uncovering-tumor-promoting-roles-of-activin-a-in-pancreatic-ductal-adenocarcinoma/405733.png","ImageObject",300,407,{"name":92,"@type":93},"Mia  ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-28",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},"What role does activin A play in pancreatic ductal adenocarcinoma?","Question",{"text":112,"@type":113},"High circulating activin A predicts poor survival in PDAC. The study finds activin A abundantly expressed in tumor and stromal cells and supports its tumor-promoting role.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was activin A suppressed in the study?",{"text":117,"@type":113},"Activin A suppression was achieved using tumor-targeted Inhba siRNA delivered by cholesterol-modified polymeric nanoparticles in orthotopic male mice.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular and cellular changes occur after activin A suppression?",{"text":121,"@type":113},"Activin A suppression decreases the proliferation marker Ki67 and is associated with increased accumulation of α-SMAhigh fibroblasts and cytotoxic T cells in tumors.","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},405733,1790867944,{"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,"preview_page_count":4},687207024478,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nUncovering Tumor-Promoting Roles ofActivin A in Pancreatic Ductal Adenocarcinoma  \nSeok-Yeong Yu, Yi Luan, Siyuan Tang, Amirhossein Abazarikia, Rosemary Dong, Thomas C. Caffrey, Michael A. Hollingsworth, David Oupicky, and So-Youn Kim*  \nPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with high incidence rates of metastasis and cachexia. High circulating activin A, a homodimer ofinhibin 􀀂A subunits that are encoded by INHBA gene, predicts poor survival among PDAC patients. However, it still raises the question of whether activin A suppression renders favorable PDAC outcomes. Here, the authors demonstrate that activin A is abundantly detected in tumor and stromal cells on PDAC tissue microarray and mouse PDAC sections. In orthotopic male mice, activin A suppression, which is acquired by  \ntumor-targeted Inhba siRNA using cholesterol-modified polymeric nanoparticles, retards tumor growth/metastasis and cachexia and improves survival when compared to scramble siRNA-treated group. Histologically, activin A suppression coincides with decreased expression of proliferation marker Ki67 but increased accumulation of 􀀃-SMAhigh fibroblasts and cytotoxic T cells in the tumors. In vitro data demonstrate that activin A promotes KPC cell proliferation and induces the downregulation of 􀀃-SMA and upregulation of IL-6 in pancreatic stellate cells (PSC) in the  \nSMAD3-dependent mechanism. Moreover, conditioned media from activin A-stimulated PSC promoted KPC cell growth. Collectively, our data provide a mechanistic basis for tumor-promoting roles ofactivin A and support therapeutic potentials of tumor activin A suppression for PDAC.  \napproximately 10% 5-year relative survival rates and is the third leading cause of cancer-related deaths in the US.[2] The dismal prognosis pertains to few early diagnostic tools, chemoresistance, and high incidence of comorbidities including cachexia.[3] Therefore, more efforts are needed towards improving PDAC prognosis by identifying prognostic factors for PDAC and their underlying mechanisms.[4] Inhibin 􀀂A (INHBA) is a subunit of activins and inhibin A which are members of the transforming growth factor 􀀂 family (TGF-􀀂) . The homodimer ofinhibin 􀀂A subunits constitutes activin A, and inhibin 􀀂A and inhibin 􀀂B (INHBB) form activin AB. Inhibin 􀀂A also heterodimerizes withinhibin 􀀃 (INHA) to make inhibin A which antagonizes activin A by competing for Activin receptors.[5] Activin A was first discovered from the porcine follicular fluidas an ovarian hormone.[6] Activin A acts through its binding to activin type 2 receptors (ACVR2A or ACVR2B), which recruits type 1 receptors to form a receptor complex.[7] Then, intracellular signaling  \n1. Introduction  \nPancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer. KRAS mutations are present in nearly 95% of PDAC tumors and co-present with TP53 mutation in approximately 70% of PDAC tumors.[1] PDAC has  \ntransductions are mediated by two pathways: the canonical pathway, where SMAD3 is phosphorylated and recruits SMAD4 to acquire transcriptional activity, and the noncanonical pathway, where subfamilies of the mitogen-activated protein kinases including p38 activate downstream molecules.[8] SMAD3-dependent signaling is indispensable for the proliferation of ovarian granulosa cells by activinA, and the downstream targets, Inha  \nS.-Y. Yu, Y. Luan, A. Abazarikia, R. Dong, S.-Y. Kim  \nOlson Center for Women’s Health Department of Obstetrics and Gynecology College of Medicine  \nUniversity of Nebraska Medical Center Omaha, NE USA  \nE-mail: [soyoun.kim@unmc.edu](soyoun.kim@unmc.edu)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202207010](https://doi.org/10.1002/advs.202207010)[ ](https://doi.org/10.1002/advs.202207010)© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. ","cbCaijcQyTB7HLtX","https://ap.wps.com/l/cbCaijcQyTB7HLtX","pdf",7618766,13,"English","# Introduction\n## Activin A in PDAC and prognostic background\n## Study rationale and therapeutic question\n## Signaling pathways and receptor mechanism","[{\"question\":\"What role does activin A play in pancreatic ductal adenocarcinoma?\",\"answer\":\"High circulating activin A predicts poor survival in PDAC. The study finds activin A abundantly expressed in tumor and stromal cells and supports its tumor-promoting role.\"},{\"question\":\"How was activin A suppressed in the study?\",\"answer\":\"Activin A suppression was achieved using tumor-targeted Inhba siRNA delivered by cholesterol-modified polymeric nanoparticles in orthotopic male mice.\"},{\"question\":\"What molecular and cellular changes occur after activin A suppression?\",\"answer\":\"Activin A suppression decreases the proliferation marker Ki67 and is associated with increased accumulation of α-SMAhigh fibroblasts and cytotoxic T cells in tumors.\"}]","Uncovering Tumor-Promoting Roles of Activin A in Pancreatic Ductal Adenocarcinoma | PDF",1790561628,33]