[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-340640-105":59,"doc-detail-340640-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","perinuclear-assembly-of-vimentin-intermediate-filaments-induces-cancer-cell-nuclear-dysmorphia","Perinuclear assembly of vimentin intermediate filaments induces cancer cell nuclear dysmorphia","","Nuclear dysmorphia—crumpled or lobulated polymorphic nuclear shapes—is used to assess malignant grades, yet the contribution of vimentin remained unclear. This research shows vimentin intermediate filaments (VIFs) frequently accumulate at the concave region of dysmorphic nuclei in breast cancer MDA-MB-231 cells. Vimentin depletion restores nuclear shape and prevents re-expression-driven deformation, whereas an assembly-defective mutant fails to rescue. Plectin depletion partially reduces perinuclear VIF buildup and nuclear dysmorphia, and VIF depletion blocks EMT-driven nuclear distortion in A549 lung cancer cells. VIF-mediated dysmorphia also compromises DNA repair, linking these changes to genome instability.",{"@graph":69,"@context":123},[70,84,106],{"@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/perinuclear-assembly-of-vimentin-intermediate-filaments-induces-cancer-cell-nuclear-dysmorphia/340640/",{"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/perinuclear-assembly-of-vimentin-intermediate-filaments-induces-cancer-cell-nuclear-dysmorphia/340640.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is nuclear dysmorphia and why is it important in cancer?","Question",{"text":113,"@type":114},"Nuclear dysmorphia refers to crumpled or lobulated polymorphic nuclear shapes. It is used as an index for malignant grades in certain cancers and is associated with genome integrity defects.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do vimentin intermediate filaments affect cancer cell nuclear shape?",{"text":118,"@type":114},"Vimentin intermediate filaments frequently accumulate at the concave of dysmorphic nuclei. Depleting vimentin restores nuclear shape, while re-expression of vimentin disrupts nuclear morphology.",{"name":120,"@type":111,"acceptedAnswer":121},"What relationship does VIF-mediated dysmorphia have with DNA repair?",{"text":122,"@type":114},"The study reports that VIF-mediated nuclear dysmorphia leads to defects in DNA repair, connecting nuclear shape abnormalities with genome instability.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},340640,1790217909,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","RESEARCH ARTICLE  \nPerinuclear assembly of vimentin intermediate filaments induces cancer cell nuclear dysmorphia  \nReceived for publication, May 23, 2024, and in revised form, October 15, 2024 Published, Papers in Press, November 13, 2024, [https://doi.org/10.1016/j.jbc.2024.107981](https://doi.org/10.1016/j.jbc.2024.107981)  \nKe-Wei Pan 1 and Hong-Chen Chen 1,2,3, *  \nFrom the 1Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan; 2Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan  \nReviewed by members of the JBC Editorial Board. Edited by Enrique De La Cruz  \nNuclear dysmorphia, characterized by crumpled or lobulated polymorphic nuclear shapes, has been used as an index for the malignant grades of certain cancers. The expression of vimentin, a type-III intermediate filament protein, is a hallmark of the epithelial-to-mesenchymal transition. However, it remains unclear whether vimentin is involved in cancer cell nuclear dysmorphia. In this study, we found that vimentin intermediate filaments (VIFs) frequently accumulated at the concave of dysmorphic nucleus in breast cancer MDA-MB- 231 cells. Depletion of vimentin apparently restored the nuclear shape of the cells, which was devastated by re-expression of vimentin, but not its assembly-defective Y117D mutant. Depletion of plectin, a cytoskeletal linker, partially prevented the perinuclear accumulation of VIFs and concomitantly restored the nuclear shape of the cells. In addition, depletion of vimentin in lung cancer A549 cells largely prevented nuclear dysmorphia during the epithelial-to-mesenchymal transition induced by TGFb. Moreover, we found that VIF-mediated nuclear dysmorphia led to defects in DNA repair. Together, our results unveil a novel role of VIFs in cancer cell nuclear dysmorphia, which is associated with genome instability.  \nThe mammalian cell nucleus usually exhibits as a spheroid or ellipsoid shape. However, some cancer cells display crumpled or lobulated polymorphic nuclear shapes, termed nuclear dysmorphia. Nuclear dysmorphia has been applied to clinical diagnosis for malignant grades of certain cancers (1). Since nuclear architecture is mainly supported by the nuclear lamina, a meshwork structure near the inner nuclear membrane, the rigidity of the nuclear lamina is thought to be critical for maintenance of nuclear shape (2). The nuclear lamina is composed of lamins (type V intermediate filament proteins) and nuclear membrane-associated proteins (3). Its integrity and rigidity can be affected by expression, post-translational modification, and mutation of lamins. Downregulation of lamin A has been shown to cause nuclear deformation in lung and breast cancer cells (4, 5). In most cases, phosphorylation of lamins at specific serine and tyrosine residues has an adverse effect on their assembly (6–8). The mutations in the LMNA  \n* For correspondence: Hong-Chen Chen, [hcchen1029@nycu.edu.tw](hcchen1029@nycu.edu.tw).  \ngene cause a group of rare genetic disorders collectively called laminopathies (9). The cells derived from laminopathy patients display defects in the nuclear lamina organization and nuclear dysmorphia (10, 11).  \nDecreased rigidity of the nuclear lamina caused by defects in the nuclear lamina organization can render the nucleus susceptible to deformation by mechanical forces that directly apply to the nucleus. The forces that affect nuclear shape can arise from both outside and inside the nucleus. Outside the nucleus, the unrestrained actomyosin-mediated contractility was reported to drive cancer cell nuclear dysmorphia (12). Inside the nucleus, chromatin compaction via increased heterochromatin confers rigidity to the nucleus (13).  \nThe defects in nuclear lamina organization can induce mislocalization and/or downregulation of DNA repair proteins, suc","cbCaikwhP99vG9DO","https://ap.wps.com/l/cbCaikwhP99vG9DO","pdf",4831183,15,"English","# Introduction\n# Vimentin and nuclear dysmorphia\n# Mechanistic links to DNA repair and genome instability\n# Materials and methods\n## Cell models and experimental conditions\n## Genetic or protein depletion approaches","[{\"question\":\"What is nuclear dysmorphia and why is it important in cancer?\",\"answer\":\"Nuclear dysmorphia refers to crumpled or lobulated polymorphic nuclear shapes. It is used as an index for malignant grades in certain cancers and is associated with genome integrity defects.\"},{\"question\":\"How do vimentin intermediate filaments affect cancer cell nuclear shape?\",\"answer\":\"Vimentin intermediate filaments frequently accumulate at the concave of dysmorphic nuclei. Depleting vimentin restores nuclear shape, while re-expression of vimentin disrupts nuclear morphology.\"},{\"question\":\"What relationship does VIF-mediated dysmorphia have with DNA repair?\",\"answer\":\"The study reports that VIF-mediated nuclear dysmorphia leads to defects in DNA repair, connecting nuclear shape abnormalities with genome instability.\"}]","Perinuclear assembly of vimentin intermediate filaments induces cancer cell nuclear dysmorphia | PDF",1790037842,38]