[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-376067-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-376067-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","yaptead4sp1-induced-vista-expression-as-a-tumor-cell-intrinsic-mechanism-of-immunosuppression-in-colorectal-cancer","YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer","","Hyperactivation of the YAP/TEAD transcriptional complex promotes an immunosuppressive tumor microenvironment. SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer, and PKCζ phosphorylates SP1 after serum stimulation to enhance TEAD4 binding. The SP1-YAP/TEAD4 complex directly upregulates VISTA in CRC cells, suppressing CD8+ T-cell antitumor function and correlating with poor prognosis. A deglycosylation approach improves anti-VISTA antibody detection in clinical samples.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/yaptead4sp1-induced-vista-expression-as-a-tumor-cell-intrinsic-mechanism-of-immunosuppression-in-colorectal-cancer/376067/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/yaptead4sp1-induced-vista-expression-as-a-tumor-cell-intrinsic-mechanism-of-immunosuppression-in-colorectal-cancer/376067.png","ImageObject",300,407,{"name":42,"@type":43},"Chumphorn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does SP1 influence YAP/TEAD activity in colorectal cancer?","Question",{"text":63,"@type":64},"SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci, and it enhances YAP/TEAD transcriptional activity together with TEAD4.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does VISTA play in tumor immune evasion according to the study?",{"text":68,"@type":64},"YAP-induced VISTA upregulation in colorectal cancer strongly suppresses the antitumor function of CD8+ T cells, supporting a mechanism of immune evasion.",{"name":70,"@type":61,"acceptedAnswer":71},"Why was enzymatic deglycosylation used in clinical sample analysis?",{"text":72,"@type":64},"Enzymatic deglycosylation significantly improves the anti-VISTA antibody signal intensity, enabling more accurate detection of VISTA in clinical tumor samples.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},376067,1790636785,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","[www.nature.com/cdd](www.nature.com/cdd)  \nARTICLE OPEN   \nYAP/TEAD4/SP1-induced VISTA expression as a tumor cellintrinsic mechanism of immunosuppression in colorectal cancer  \nZhehui Zhu1,2,3,4, Rui Ding 1,3,4, Wei Yu 2, Yun Liu 1,3 ✉, Zhaocai Zhou 2 ✉ 1,3 ✉  \nand Chen-Ying Liu  \n© The Author(s) 2025  \n|  |  |  |\n| --- | --- | --- |\n|  | Hyperactivation of the YAP/TEAD transcriptional complex in cancers facilitates the development of an immunosuppressive tumor microenvironment. Herein, we observed that the transcription factor SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer (CRC) . In response to serum stimulation, PKCζ (protein kinase C ζ) was found to phosphorylate SP1 and enhance its interaction with TEAD4 . As a result, SP1 enhanced the transcriptional activity of YAP/ TEAD and coregulated the expression of a group of YAP/TEAD target genes. The immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) was identified as a direct target of the SP1-YAP/TEAD4 complex and found to be widely expressed in CRC cells. Importantly, YAP-induced VISTA upregulation in human CRC cells was found to strongly suppress the antitumor function of CD8+ T cells. Consistently, elevated VISTA expression was found to be correlated with hyperactivation of the SP1-YAP/TEAD axis and associated with poor prognosis of CRC patients. In addition, we found by serendipity that enzymatic deglycosylation significantly improved the anti-VISTA antibody signal intensity, resulting in more accurate detection of VISTA in clinical tumor samples. Overall, our study identified SP1 as a positive modulator of YAP/TEAD for the transcriptional regulation of VISTA and developed a protein deglycosylation strategy to better detect VISTA expression in clinical samples. These findings revealed a new |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| tumor cell-intrinsic mechanism of YAP/TAZ-mediated cancer immune evasion. |  |  |\n|  | Cell Death & Differentiation (2025) 32:911–925; [https://doi.org/10.1038/s41418-025-01446-2](https://doi.org/10.1038/s41418-025-01446-2) |  |\n|  |  |  |\n\nINTRODUCTION  \nThe Hippo pathway has been identified as a key signaling pathway that plays a vital role in controlling organ size and tissue homeostasis [1, 2] . Dysregulation of the Hippo pathway has been widely observed in various cancers, including colorectal cancer (CRC) [3–5] . Activation of YAP/TAZ, the main downstream effectors of the Hippo pathway, modulates the transcription of a series of downstream target genes, mainly through cooperation with TEAD transcription factor members (TEAD1-4), and has been linked to tumor growth, survival, metastasis, and drug resistance [3–6] . Recent studies have also revealed the crucial role of YAP/TAZ in facilitating the development of an immunosuppressive tumor microenvironment (TME) [7–9] . YAP-induced expression of tumorderived cytokines enhances the recruitment of tumor-infiltrating macrophages, MDSCs and Tregs [10–12] . In addition, YAP/TAZ directly promote the transcription of the PDL1 gene, which encodes programmed cell death 1 ligand 1 expressed on the tumor cell surface, thus inducing activated T-cell apoptosis and driving immune evasion [13–15] . Although the regulatory axis of YAP/TAZ-PDL1 has been shown in breast, lung and melanoma cancer cell lines, the biological relevance of the YAP/TAZ-PDL1 axis may be dependent on the cell context and has not been studied in traditional syngeneic or genetically engineered mouse models [7–9] .  \nV-domain Ig suppressor of T-cell activation (VISTA), which is encoded by the VSIR or C10ORF54 gene, is a B7 family member that maintains T-cell quiescence and mediates the immunoinhibitory function of myeloid-derived suppressor cells (MDSCs); therefore, VISTA is a promising immune checkpoint target for cancer immunotherapy [16–18] . VISTA has been shown to bind w","cbCaifNvgmaWRVCM","https://ap.wps.com/l/cbCaifNvgmaWRVCM","pdf",5410183,15,"English","# Introduction\n## Hippo pathway and YAP/TAZ in cancer immunosuppression\n## VISTA biology and relevance to cancer therapy","[{\"question\":\"How does SP1 influence YAP/TEAD activity in colorectal cancer?\",\"answer\":\"SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci, and it enhances YAP/TEAD transcriptional activity together with TEAD4.\"},{\"question\":\"What role does VISTA play in tumor immune evasion according to the study?\",\"answer\":\"YAP-induced VISTA upregulation in colorectal cancer strongly suppresses the antitumor function of CD8+ T cells, supporting a mechanism of immune evasion.\"},{\"question\":\"Why was enzymatic deglycosylation used in clinical sample analysis?\",\"answer\":\"Enzymatic deglycosylation significantly improves the anti-VISTA antibody signal intensity, enabling more accurate detection of VISTA in clinical tumor samples.\"}]","YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer | PDF",1790217168,38]