[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330425-105":59,"doc-detail-330425-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","hippo-signaling-at-the-hallmarks-of-cancer-and-drug-resistance-review","Hippo Signaling at the Hallmarks of Cancer and Drug Resistance - Review","","Originally identified in Drosophila melanogaster in 1995, the Hippo signaling pathway controls organ size and suppresses tumors by limiting proliferation and promoting apoptosis. Large tumor suppressors LATS1/2 phosphorylate YAP and TAZ, restricting their nuclear localization and TEAD coactivator interactions. Dysregulated Hippo signaling contributes to tumorigenesis, EMT, oncogenic stemness, and emerging drug resistance. This review emphasizes Hippo cross-talk with other oncogenic drivers and translates the mechanism into combination therapy strategies for aggressive cancers.",{"@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/hippo-signaling-at-the-hallmarks-of-cancer-and-drug-resistance-review/330425/",{"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/hippo-signaling-at-the-hallmarks-of-cancer-and-drug-resistance-review/330425.png","ImageObject",300,407,{"name":92,"@type":93},"Ava Thompson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",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 is the main function of the Hippo signaling pathway in cancer biology?","Question",{"text":112,"@type":113},"Hippo signaling regulates organ size and tumor suppression by inhibiting proliferation and promoting apoptosis through control of YAP/TAZ activity and localization.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do LATS1/2 affect YAP and TAZ?",{"text":117,"@type":113},"LATS1/2 directly phosphorylate YAP and TAZ, which inhibits their nuclear localization and prevents productive pairing with TEAD1-4 transcriptional coactivators.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is Hippo signaling relevant to drug resistance?",{"text":121,"@type":113},"Mis-regulated Hippo signaling supports oncogenic adaptations, and Hippo components at the center of these adaptations contribute to development of drug resistance, including in targeted therapy contexts.","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},330425,1790499193,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"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},1649267921044,"https://us-avatar.wpscdn.com/avatar/1800007509477c92dfb?_k=1786009248482753345","cells  \nReview  \nHippo Signaling at the Hallmarks of Cancer and Drug Resistance Ramesh Kumar * and Wanjin Hong  \nCitation: Kumar, R.; Hong, W. Hippo Signaling at the Hallmarks of Cancer and Drug Resistance. Cells 2024, 13, 564. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13070564  \nAcademic Editor: Birgit Leitinger  \nReceived: 8 January 2024  \nRevised: 11 March 2024  \nAccepted: 20 March 2024  \nPublished: 22 March 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nInstitute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology, and Research), Singapore 138673, Singapore; [mcbhwj@imcb.a-star.edu.sg](mcbhwj@imcb.a-star.edu.sg)  \n* Correspondence: [ramesh_kumar@imcb.a-star.edu.sg](ramesh_kumar@imcb.a-star.edu.sg)  \nAbstract: Originally identified in Drosophila melanogaster in 1995, the Hippo signaling pathway plays a pivotal role in organ size control and tumor suppression by inhibiting proliferation and promoting apoptosis. Large tumor suppressors 1 and 2 (LATS1/2) directly phosphorylate the Yki orthologs YAP (yes-associated protein) and its paralog TAZ (also known as WW domain-containing transcription regulator 1 [WWTR1]), thereby inhibiting their nuclear localization and pairing with transcriptional coactivators TEAD1-4 . Earnest efforts from many research laboratories have established the role of mis-regulated Hippo signaling in tumorigenesis, epithelial mesenchymal transition (EMT), oncogenic stemness, and, more recently, development of drug resistances. Hippo signaling components atthe heart of oncogenic adaptations fuel the development of drug resistance in many cancers for targeted therapies including KRAS and EGFR mutants. The first U.S. food and drug administration (US FDA) approval of the imatinib tyrosine kinase inhibitor in 2001 paved the way for nearly 100 small-molecule anti-cancer drugs approved by the US FDA and the national medical products administration (NMPA) . However, the low response rate and development of drug resistance have posed a major hurdle to improving the progression-free survival (PFS) and overall survival (OS) of cancer patients. Accumulating evidence has enabled scientists and clinicians to strategize the therapeutic approaches of targeting cancer cells and to navigate the development of drug resistance through the continuous monitoring of tumor evolution and oncogenic adaptations. In this review, we highlight the emerging aspects of Hippo signaling in cross-talk with other oncogenic drivers and how this information can be translated into combination therapy to target a broad range of aggressive tumors and the development of drug resistance.  \nKeywords: hippo signaling; carcinogenesis; cancer; KRAS; EGFR; drug resistance; combination therapy  \n1. Introduction  \nOriginally identified and described in Drosophila melanogaster, principal components of the mammalian Hippo signaling pathway have been conserved. During the past 15 years, the area has received a wider investigation due to key regulatory roles in development, regeneration, as well as pro-cancerous functions. Key components of the mammalian Hippo signaling pathway consist of mammalian Ste20-like kinases 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), yes-associated protein (YAP), and/or its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) encoded by the WW domain-containing transcription regulator 1 (WWTR1) gene. Upon physiological and/or pathological signalinduced activation of the upstream components, the MST1/2 (Hippo/Hpo) forms a complex with the adaptor protein Salvador 1 (SAV1), which acts to phosphorylate and activate the large tumor suppress","cbCaidkLHplxgdbD","https://ap.wps.com/l/cbCaidkLHplxgdbD","pdf",2317912,13,"English","# Introduction\n## Core Hippo signaling components and regulation\n## Downstream transcriptional control\n## Post-translational modifications and interaction networks","[{\"question\":\"What is the main function of the Hippo signaling pathway in cancer biology?\",\"answer\":\"Hippo signaling regulates organ size and tumor suppression by inhibiting proliferation and promoting apoptosis through control of YAP/TAZ activity and localization.\"},{\"question\":\"How do LATS1/2 affect YAP and TAZ?\",\"answer\":\"LATS1/2 directly phosphorylate YAP and TAZ, which inhibits their nuclear localization and prevents productive pairing with TEAD1-4 transcriptional coactivators.\"},{\"question\":\"Why is Hippo signaling relevant to drug resistance?\",\"answer\":\"Mis-regulated Hippo signaling supports oncogenic adaptations, and Hippo components at the center of these adaptations contribute to development of drug resistance, including in targeted therapy contexts.\"}]","Hippo Signaling at the Hallmarks of Cancer and Drug Resistance - Review | PDF",1789988850,33]