[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-350514-105":59,"doc-detail-350514-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","characterization-of-adgrg6-as-a-potential-molecular-oncotarget-of-pancreatic-cancer","Characterization of ADGRG6 as a potential molecular oncotarget of pancreatic cancer","","Identifying novel therapeutic targets for pancreatic cancer (PC) is crucial for improving patient outcomes. This study characterized adhesion G protein-coupled receptor G6 (ADGRG6/GPR126) by integrating expression profiling and functional assays. Bioinformatics analyses showed ADGRG6 upregulation in PC, linked to worse survival and advanced stages. ADGRG6 depletion using CRISPR/Cas9 knockout or lentiviral shRNA reduced proliferation, viability, and migration/invasion, while overexpression enhanced malignancy. Mechanistically, ADGRG6 promoted Akt-mTOR activation via Gαi3, and inhibition suppressed xenograft growth in mice.",{"@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/characterization-of-adgrg6-as-a-potential-molecular-oncotarget-of-pancreatic-cancer/350514/",{"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/characterization-of-adgrg6-as-a-potential-molecular-oncotarget-of-pancreatic-cancer/350514.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","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},"What role does ADGRG6 play in pancreatic cancer progression?","Question",{"text":112,"@type":113},"ADGRG6 is upregulated in pancreatic cancer and is associated with poor survival and advanced tumor stages. Functional experiments show that altering ADGRG6 levels changes proliferation, viability, and metastatic behaviors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do ADGRG6 knockout or knockdown affect pancreatic cancer cells?",{"text":117,"@type":113},"CRISPR/Cas9 knockout or lentiviral shRNA depletion of ADGRG6 reduces cell cycle progression, proliferation, viability, and migration/invasion in established and primary PC cells.",{"name":119,"@type":110,"acceptedAnswer":120},"Through which signaling pathway does ADGRG6 exert its effects?",{"text":121,"@type":113},"ADGRG6 promotes activation of the Akt-mTOR cascade. ADGRG6-driven Akt-mTOR activation is mediated by G protein inhibitory subunit 3 (Gαi3), and restoring Akt activity can reverse the suppressive effects of ADGRG6 silencing.","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},350514,1790212088,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":66,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},4398046744996,"[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nCharacterization of ADGRG6 as a potential molecular oncotarget of pancreatic cancer  \nQian-hui Gu1,2,8, Xiao-ren Zhu 1,2,3,8, Jian-zhuo Jiang4,5,8, Na Liu1,2,8, An-qi Jin6, Yan Zhang 1,2, Jing-jing Lu 1,2, Ping Li 1,2, Zhen-yu Ye7 ✉, Yuan-yuan Liu 4 ✉ and Min-bin Chen 1,2 ✉  \n© The Author(s) 2026  \n\n| | Identifying novel therapeutic targets for pancreatic cancer (PC) is crucial for improving patient outcomes. This study identified the functions, expression, and associated mechanisms of adhesion G protein-coupled receptor G6 (ADGRG6/ GPR126) in PC. Bioinformatics analyses revealed substantial upregulation of ADGRG6 in human PC, correlating with poor survival rates and advanced tumor stages. Elevated ADGRG6 expression has been observed in human PC tissues and cell lines. Targeted depletion of ADGRG6 via the CRISPR/Cas9 knockout (KO) or lentiviral shRNA technology in established and primary PC cells (priPC-1) resulted ina substantial decrease in cell cycle progression, cell proliferation, viability, as well as reduced migratory and invasive capabilities. Conversely, ADGRG6 overexpression further enhanced the malignant behavior of PC cells. Mechanistically, ADGRG6 is crucial for Akt-mTOR cascade activation. ADGRG6 depletion markedly decreased Akt, S6, and 4E-BP1 phosphorylation. Constitutively active mutant Akt1 (S473D, caAkt1) reversed the anti-proliferative and anti-migratory effects of ADGRG65 shRNA and restored Akt-mTOR phosphorylation. Further analysis revealed that ADGRG6-driven Akt-mTOR activation is mediated by G protein inhibitory subunit 3\u003Cbr>(Gαi3) . ADGRG6 shRNA significantly inhibited subcutaneous PC xenograft growth in mice, accompanied by reduced Akt-mTOR signaling activation. In contrast, ADGRG6 overexpression promotes xenograft growth. Together, these findings establish ADGRG6 asa critical mediator of PC progression via Gαi3-dependent activation of the Akt-mTOR axis. Targeting ADGRG6 is a promising | |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | therapeutic strategy for combating PC. |  |\n|  |  |  |\n|  |  |  |\n|  | Cell Death and Disease (2026)17:604; [https://doi.org/10.1038/s41419-026-08766-2](https://doi.org/10.1038/s41419-026-08766-2) |  |\n|  |  |  |\n\nINTRODUCTION  \nPancreatic cancer (PC) is a highly lethal malignancy with a five-year survival rate of less than 10%[1, 2]. Recurrence rates in patients with early-stage PC range from 50 to 70% within one year following surgery [3]. The poor prognosis associated with PC is primarily due to late diagnosis, distant metastases, and intrinsic resistance to conventional treatment modalities [4]. Chemotherapy regimens incorporating irinotecan liposomes or gemcitabine are the standard first-line treatments for advanced PC [5–7]. However, their clinical utility is significantly hindered by poor patient tolerance, as well asthe systemic and multifocal characteristics of advanced disease, which collectively diminish the efficacy of systemic intravenous chemotherapy [8, 9]. Furthermore, the therapeutic outcomes of immunotherapy and radiotherapy for PC remain unsatisfactory [2]. Therefore, a deeper insight into the molecular mechanisms underlying PC progression is crucial for identifying and developing effective targeted treatments.  \nG-protein-coupled receptors (GPCRs), a fundamental and highly diverse superfamily of membrane-bound proteins  \nmediating signal transduction, have been increasingly recognized for their pivotal roles in tumorigenesis and cancer progression [10, 11] . Aberrant expression of specific GPCRs is observed across a range of cancer types, where these dysregulated receptors are implicated in key processes, such as cell transformation, proliferation, angiogenesis, metastasis, drug resistance, and apoptosis [12, 13] . Importantly, GPCRs and their associated signaling pathways are ","cbCaiurV2iVTqhQ4","https://ap.wps.com/l/cbCaiurV2iVTqhQ4","pdf",12374299,18,"English","# Introduction\n# Methods and Results\n# ADGRG6 expression and clinical relevance\n# Functional effects of ADGRG6 perturbation\n# ADGRG6–Gαi3–Akt-mTOR mechanism\n# Xenograft validation in mice","[{\"question\":\"What role does ADGRG6 play in pancreatic cancer progression?\",\"answer\":\"ADGRG6 is upregulated in pancreatic cancer and is associated with poor survival and advanced tumor stages. Functional experiments show that altering ADGRG6 levels changes proliferation, viability, and metastatic behaviors.\"},{\"question\":\"How do ADGRG6 knockout or knockdown affect pancreatic cancer cells?\",\"answer\":\"CRISPR/Cas9 knockout or lentiviral shRNA depletion of ADGRG6 reduces cell cycle progression, proliferation, viability, and migration/invasion in established and primary PC cells.\"},{\"question\":\"Through which signaling pathway does ADGRG6 exert its effects?\",\"answer\":\"ADGRG6 promotes activation of the Akt-mTOR cascade. ADGRG6-driven Akt-mTOR activation is mediated by G protein inhibitory subunit 3 (Gαi3), and restoring Akt activity can reverse the suppressive effects of ADGRG6 silencing.\"}]","Characterization of ADGRG6 as a potential molecular oncotarget of pancreatic cancer | PDF",1790089379,45]