[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-328939-105":59,"doc-detail-328939-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","non-canonical-olfactory-pathway-activation-induces-cell-fusion-of-cervical-cancer-cells","Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells","","Multinucleation is a hallmark of advanced cancers and promotes malignancy, including anticancer drug resistance, yet its molecular basis remains unclear. This study introduces a genetic mutation in cervical cancer cells to drive cell fusion–mediated multinucleation. The mutated olfactory receptor OR1N2 activates protein kinase A (PKA), which phosphorylates and activates furin to cleave syncytin-1. Furin inhibition suppresses multinucleation and decreases surviving cells after drug treatment, supporting a therapeutic strategy for advanced cervical 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":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/non-canonical-olfactory-pathway-activation-induces-cell-fusion-of-cervical-cancer-cells/328939/",{"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/non-canonical-olfactory-pathway-activation-induces-cell-fusion-of-cervical-cancer-cells/328939.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","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 approach was used to induce cell fusion–mediated multinucleation in cervical cancer cells?","Question",{"text":112,"@type":113},"The study introduced a genetic mutation in cervical cancer cells to induce cell fusion–mediated multinucleation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the OR1N2 mutation connect to the non-canonical olfactory pathway?",{"text":117,"@type":113},"The mutation causes a structural change in OR1N2 that activates protein kinase A (PKA), which then mediates the non-canonical olfactory pathway.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are furin inhibitors predicted to improve anticancer drug responses?",{"text":121,"@type":113},"PKA activation leads to furin-mediated cleavage of syncytin-1, which participates in cell fusion; inhibiting furin suppresses multinucleation and reduces surviving cell numbers after anticancer treatment.","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},328939,1790108334,{"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},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Neoplasia 57 (2024) 101044  \nContents lists available at ScienceDirect  \nNeoplasia  \njournal [homepage:](homepage: www.elsevier.com/locate/neo)[ www.elsevier.com/locate/neo](homepage: www.elsevier.com/locate/neo)  \n| Original Research\u003Cbr>Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells |  |  | |\n| --- | --- | --- | --- |\n| Keigo Arakia,*, Takeru Toriib, Kohei Takeuchi b, Natsuki Kinoshita b, Ryoto Uranob, Rinka Nakajima c, Yaxuan Zhou c, Tokuo Kobayashi a, Tadayoshi Hanyu d, Kiyoshi Ohtani c, Kimiharu Ambea, Keiko Kawauchib\u003Cbr>a Department of Morphological Biology, School of Dentistry, Ohu University, Koriyama, Fukushima 963-8611, Japan b Frontiers of Innovative Research in Science and Technology, Konan University, Kobe, Hyogo 650-0047, Japan\u003Cbr>c Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Hyogo 669-1330, Japan d Department of Gynecology, Tsuboi Cancer Center Hospital, Koriyama, Fukushima 963-0197, Japan |  |  |  |\n| A R T I C L E I N F O |  | A B S T R A C T |  |\n| Keywords:\u003Cbr>Cervical cancer\u003Cbr>Cell fusion\u003Cbr>Olfactory pathway Anticancer drug resistance PKA\u003Cbr>Furin |  | Multinucleation occurs in various types of advanced cancers and contributes to their malignant characteristics, including anticancer drug resistance. Therefore, inhibiting multinucleation can improve cancer prognosis; however, the molecular mechanisms underlying multinucleation remain elusive. Here, we introduced a genetic mutation in cervical cancer cells to induce cell fusion-mediated multinucleation. The olfactory receptor OR1N2 was heterozygously mutated in these fused cells; the same OR1N2 mutation was detected in multinucleated cells from clinical cervical cancer specimens. The mutation-induced structural change in the OR1N2 protein activated protein kinase A (PKA), which, in turn, mediated the non-canonical olfactory pathway. PKA phosphorylated and activated furin protease, resulting in the cleavage of the fusogenic protein syncytin-1. Because this cleaved form of syncytin-1, processed by furin, participates in cell fusion, furin inhibitors could suppress multinucleation and reduce surviving cell numbers after anticancer drug treatment. The improved anticancer drug efficacy indicates a promising therapeutic approach for advanced cervical cancers. |  |\n\nIntroduction  \nCancer is a group of diseases that exhibits a variety of undesirable cellular characteristics, most typically uncontrolled cellular proliferation [1,2]. Given that cancer cells can uncontrollably invade and metastasize to other parts of the human body, appropriate cancer management is crucial for improving treatment outcomes. Cancer is a fundamental consequence of genetic mutations [3] that can occur spontaneously or be triggered by environmental factors, including synthetic chemicals, non-ionizing radiation, and infectious agents such as oncoviruses [4,5]. Various types of genetic mutations, such as chromosomal deletions, duplications, and translocations, can be related to cancer initiation [6]; however, point mutations are the most frequent genetic mutations and alter protein functions. Cancer initiation is a complex biological process, and a combination of mutations in specific  \ngenes, such as oncogenes and tumor suppressor genes, often leads to cancer onset [3]. Genetic mutations play crucial roles in cancer progression as well as initiation [7-9]. Cancers are heterogeneous, with various subpopulations of cells and additional mutations driving clonal evolution, and aggressive clones can outcompete others and develop into advanced cancers. The accumulation of more mutations during cancer progression enhances malignant characteristics, such as metastasis, invasion, and angiogenesis [7-9]. These mutations can render cancer cells resistant to chemotherapy and targeted therapies [8]. Intracellular signaling pathways induced by these mutations contribute to the malignant chara","cbCaigEQbd2o2zPC","https://ap.wps.com/l/cbCaigEQbd2o2zPC","pdf",11699039,11,"English","# Introduction\n# Abbreviations\n# Results and Discussion\n# Materials and Methods\n# Conclusion","[{\"question\":\"What approach was used to induce cell fusion–mediated multinucleation in cervical cancer cells?\",\"answer\":\"The study introduced a genetic mutation in cervical cancer cells to induce cell fusion–mediated multinucleation.\"},{\"question\":\"How does the OR1N2 mutation connect to the non-canonical olfactory pathway?\",\"answer\":\"The mutation causes a structural change in OR1N2 that activates protein kinase A (PKA), which then mediates the non-canonical olfactory pathway.\"},{\"question\":\"Why are furin inhibitors predicted to improve anticancer drug responses?\",\"answer\":\"PKA activation leads to furin-mediated cleavage of syncytin-1, which participates in cell fusion; inhibiting furin suppresses multinucleation and reduces surviving cell numbers after anticancer treatment.\"}]","Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells | PDF",1789981714,28]