[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-385669-105":59,"doc-detail-385669-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","increased-retinoic-acid-signaling-decreases-lung-metastasis-in-salivary-adenoid-cystic-carcinoma-by-inhibiting-the-noncanonical-notch1-pathway","Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway","","Salivary adenoid cystic carcinoma (SACC) commonly metastasizes to the lung and has limited therapeutic options, prompting investigation of metastasis mechanisms. This study analyzes two SACC patients lacking MYB-NFIB fusion and NOTCH1 mutation using single-cell RNA sequencing and exome target capture sequencing to map cancer cell states and pathway enrichment. Retinoic acid (RA) is identified as an endogenous antagonist of MYC_TARGETS_V2 via NICD1-MYB-MYC complex evidence, and all-trans retinoic acid suppresses lung metastasis by correcting erroneous differentiation. Bioinformatics, RNA-seq, and IHC suggest RA system insufficiency partially promotes metastasis, highlighting diagnostic and treatment value.",{"@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/increased-retinoic-acid-signaling-decreases-lung-metastasis-in-salivary-adenoid-cystic-carcinoma-by-inhibiting-the-noncanonical-notch1-pathway/385669/",{"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/increased-retinoic-acid-signaling-decreases-lung-metastasis-in-salivary-adenoid-cystic-carcinoma-by-inhibiting-the-noncanonical-notch1-pathway/385669.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the study’s main goal for salivary adenoid cystic carcinoma lung metastasis?","Question",{"text":112,"@type":113},"To clarify molecular mechanisms driving lung metastasis in SACC, focusing on retinoic acid signaling and its relationship with noncanonical Notch1 activity.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did researchers profile tumors in cases without MYB-NFIB fusion and NOTCH1 mutation?",{"text":117,"@type":113},"They used single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing to identify cell populations and analyze signaling and differentiation trajectories.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does retinoic acid signaling play in lung metastasis according to the findings?",{"text":121,"@type":113},"Retinoic acid system insufficiency partially promotes lung metastasis, while all-trans retinoic acid suppresses metastasis by correcting aberrant cell differentiation linked to NOTCH1 or MYB expression.","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},385669,1790658958,{"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":52,"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},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","[www.nature.com/emm](www.nature.com/emm)  \nARTICLE OPEN   \nIncreased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting thenoncanonical Notch1 pathway  \nMeng-jiao Zhou1,2,6, Jia-jie Yang3,6, Ting-yao Ma 1,6, Ge-xuan Feng3, Xue-lian Wang 1, Li-Yong Wang4, Yu-ze Ge3, Ran Gao2, Hong-liang Liu5, Lin Shan3, Lu Kong3 ✉ and Xiao-hong Chen1 ✉  \n© The Author(s) 2023  \n|  |  |  |\n| --- | --- | --- |\n|  | MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC) . However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from nearnormal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the “MYC_TARGETS_V2” gene set. In vitro, we detected the NICD1-MYB-MYC complex by coimmunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the“MYC_TARGETS_V2” gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| treatment. |  |  |\n|  | Experimental & Molecular Medicine (2023) 55:597–611; [https://doi.org/10.1038/s12276-023-00957-7](https://doi.org/10.1038/s12276-023-00957-7) |  |\n|  |  |  |\n\nINTRODUCTION  \nSalivary gland adenoid cystic carcinoma (SACC) has a poor clinical prognosis and a high risk of distant metastasis, most commonly to the lung1–3, and the 3-year lung metastasis rate can reach 24 .9%1. The ten-year overall survival rate of patients with aggressive SACC ranges from approximately 29 to 37%3,4, and the median survival time of patients with lung metastatic SACC is only 20–32 months5. To date, there are no available treatments for metastatic SACC6, and in-depth exploration of the underlying mechanisms is a priority for this field.  \nAberrant overexpression of MYB, NOTCH1 intracellular structural domain (NICD1), and MYC are common molecular events in SACC; MYC and NOTCH1 overexpression are mainly caused by genetic abnormalities7–12. However, approximately half of the cases show MYB activation in the absence of MYB fusion13, and the related mechanism remains unclear. All-trans retinoic acid (ATRA), an efficient inhibitor of MYB, induces the elevation of retinoic acid  \nreceptor α (RARα) and subsequently binds the MYB enhancer locus to repress MYB transcription or disrupt the MYB positive feedback loop14; it was recently considered to be a promising drug for aggressive SACC therapy14, 15. Controversially, MYB fusion and upregulation are not associated with the overall survival rate16, whilst activating mutations in NOTCH1 and the overexpression of MYC or MYC targets have been associated with worse outcomesand decreased overall survival i","cbCaibi3Iyzt87Tq","https://ap.wps.com/l/cbCaibi3Iyzt87Tq","pdf",7819562,15,"English","# Introduction\n## Retinoic acid and key molecular events in SACC\n# Methods and experimental approach\n## Single-cell RNA sequencing and exome target capture sequencing\n## Co-immunoprecipitation, RNA-seq, and immunohistochemistry\n# Findings\n## Cancer cell staging and Notch signaling enrichment\n## NICD1-MYB-MYC complex and RA as antagonist\n## ATRA effects on differentiation and lung metastasis\n# Implications","[{\"question\":\"What was the study’s main goal for salivary adenoid cystic carcinoma lung metastasis?\",\"answer\":\"To clarify molecular mechanisms driving lung metastasis in SACC, focusing on retinoic acid signaling and its relationship with noncanonical Notch1 activity.\"},{\"question\":\"How did researchers profile tumors in cases without MYB-NFIB fusion and NOTCH1 mutation?\",\"answer\":\"They used single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing to identify cell populations and analyze signaling and differentiation trajectories.\"},{\"question\":\"What role does retinoic acid signaling play in lung metastasis according to the findings?\",\"answer\":\"Retinoic acid system insufficiency partially promotes lung metastasis, while all-trans retinoic acid suppresses metastasis by correcting aberrant cell differentiation linked to NOTCH1 or MYB expression.\"}]","Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway | PDF",1790270510,38]