[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-384027-105":59,"doc-detail-384027-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","non-cell-autonomous-cancer-progression-from-chromosomal-instability-research-article-summary","Non-cell-autonomous cancer progression from chromosomal instability - Research article summary","","Chromosomal instability (CIN), a driver of cancer metastasis, is linked to cGAS–STING signaling, but its immune dependence was unclear. Using Contact Tracing from single-cell transcriptomic data, the study shows that CIN chronically activates cGAS–STING, causing cancer-cell signal re-wiring that yields a pro-metastatic tumor microenvironment. CIN reversal, STING depletion, or ER-stress inhibition suppresses CIN-dependent metastasis in immune-competent but not severely immune-compromised settings. STING inhibitors similarly reduce CIN-driven metastasis in multiple cancers. CIN and cGAS activation in micronuclei associate with ER stress, immune suppression, and metastasis in human TNBC.",{"@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/non-cell-autonomous-cancer-progression-from-chromosomal-instability-research-article-summary/384027/",{"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-cell-autonomous-cancer-progression-from-chromosomal-instability-research-article-summary/384027.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",18,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What question does the study address about chromosomal instability (CIN)?","Question",{"text":113,"@type":114},"How the metastasis-promoting effect of CIN depends on the immune system.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was cell–cell interaction information inferred in the study?",{"text":118,"@type":114},"Using Contact Tracing, a tool applied to single-cell transcriptomic data to infer interaction dependence.",{"name":120,"@type":111,"acceptedAnswer":121},"What interventions reduce CIN-driven metastasis, and under what immune conditions?",{"text":122,"@type":114},"Reversing CIN, depleting cancer-cell STING, inhibiting ER-stress signaling, or treating with STING inhibitors suppresses CIN-dependent metastasis in immune-competent but not severely immune-compromised settings.","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},384027,1790299210,{"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":36,"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},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article  \nNon-cell-autonomous cancer progression from chromosomal instability  \n\n| [https://doi.org/10.1038/s41586-023-06464-z](https://doi.org/10.1038/s41586-023-06464-z)\u003Cbr>Received: 9 December 2021 Accepted: 20 July 2023 Published online: 23 August 2023 Open access\u003Cbr> Check for updates | Jun Li1,2,14, Melissa J. Hubisz3,4,5,6,14, Ethan M. Earlie3,4,5,14, Mercedes A. Duran1,2,14,\u003Cbr>Christy Hong1,2, Austin A. Varela3,4,5, Emanuele Lettera1,2, Matthew Deyell3,4,5,\u003Cbr>Bernardo Tavora7, Jonathan J. Havel7, Su M. Phyu8, Amit Dipak Amin9,10, Karolina Budre3,4,5, Erina Kamiya3,4,5, Julie-Ann Cavallo1,2, Christopher Garris11,12, Simon Powell2,\u003Cbr>Jorge S. Reis-Filho13, Hannah Wen13, Sarah Bettigole7, Atif J. Khan2, Benjamin Izar9,10, Eileen E. Parkes8, Ashley M. Laughney3,4,5,15✉ & Samuel F. Bakhoum1,2,15✉\u003Cbr>Chromosomal instability (CIN) is adriver of cancer metastasis1–4, yet the extent to which this effect depends on the immune system remains unknown. Using Contact Tracing—a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell–cell interactions from single-cell transcriptomic data—we show that CIN-induced chronic activation of the cGAS–STING pathway promotes downstream signal re-wiring in cancer cells, leading toa pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING anda corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal ofCIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers ina manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated withER stress signalling, immune suppression and metastasis inhuman triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation. |  |\n| --- | --- | --- |\n| Chromosomal instability (CIN) is a cancer hallmark5 that is associ- |  | the effect of CINon tumour progression is cancer cell autonomous or |\n| ated with therapeutic resistance6, immune evasion7,8 and metastasis2. |  | rather dependent on the immune system. Moreover, it is unclear how |\n| CIN arises from ongoing errors in chromosome segregation during |  | chromosomally unstable tumours adapt to CIN and evade immune |\n| mitosis9,10. In normal cells, chromosome missegregation is poorly |  | surveillance that would arise from cGAS–STING activation anda down- |\n| tolerated11 and can suppress oncogenic transformation12,13. Yet, advanced human cancers are often characterized by elevated rates |  | stream type I interferon (IFN) response20. |\n| of chromosome missegregation and aneuploidy2,14,15, invoking adaptive processes that allow tumours to withstand and co-opt CIN3. Using |  | Immune dependence ofCIN-driven metastasis |\n| isogenic models that enable genetic manipulation of chromosome |  | To interrogate the influence of the immune system on CIN-driven metas- |\n| missegregation rates in cancer cells16, we have previously shown that |  | tasis, we used four syngeneic metastatic cancer models, including |\n| CIN promotes metastasis by inducing a cytosolic double-stranded DNA |  | triple-negative breast cancer (TNBC) (4T1 and EO771.LMB), colorectal |\n| (dsDNA) response in tumour cells, mediated by the cGAS–STING innate |  | adenocarcinoma (CT26) and melanoma (B16F10). All models exhibited |\n| immune pathway2. Errors in chromosome segregation lead to the for- |  | elevated rates of chromosome segregation errors during anaphase |\n| mation of rupture-prone micronuclei17 and exposure of genomic dsDNA |  | anda preponderance","cbCaivcGmwjQsyaq","https://ap.wps.com/l/cbCaivcGmwjQsyaq","pdf",58752248,"English","# Non-cell-autonomous cancer progression from chromosomal instability\n## CIN and immune dependence\n## Contact Tracing-based cell–cell interaction rewiring\n## Therapeutic implications of STING inhibition\n## Relevance to human triple-negative breast cancer","[{\"question\":\"What question does the study address about chromosomal instability (CIN)?\",\"answer\":\"How the metastasis-promoting effect of CIN depends on the immune system.\"},{\"question\":\"How was cell–cell interaction information inferred in the study?\",\"answer\":\"Using Contact Tracing, a tool applied to single-cell transcriptomic data to infer interaction dependence.\"},{\"question\":\"What interventions reduce CIN-driven metastasis, and under what immune conditions?\",\"answer\":\"Reversing CIN, depleting cancer-cell STING, inhibiting ER-stress signaling, or treating with STING inhibitors suppresses CIN-dependent metastasis in immune-competent but not severely immune-compromised settings.\"}]","Non-cell-autonomous cancer progression from chromosomal instability - Research article summary | PDF",1790260908,101]