دورية أكاديمية
أعرض في EDS

Extra centrosomes delay DNA damage-driven tumorigenesis.

التفاصيل البيبلوغرافية
العنوان: Extra centrosomes delay DNA damage-driven tumorigenesis.
المؤلفون: Braun VZ; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Karbon G; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Schuler F; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Schapfl MA; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Weiss JG; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria., Petermann PY; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Spierings DCJ; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands., Tijhuis AE; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands., Foijer F; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands., Labi V; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Villunger A; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
المصدر: Science advances [Sci Adv] 2024 Mar 29; Vol. 10 (13), pp. eadk0564. Date of Electronic Publication: 2024 Mar 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
مواضيع طبية MeSH: Centrosome* , Neoplasms*/metabolism, Humans ; Apoptosis/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; DNA Damage
مستخلص: Deregulated centrosome numbers are frequently found in human cancer and can promote malignancies in model organisms. Current research aims to clarify if extra centrosomes are cause or consequence of malignant transformation, and if their biogenesis can be targeted for therapy. Here, we show that oncogene-driven blood cancer is inert to genetic manipulation of centrosome numbers, whereas the formation of DNA damage-induced malignancies is delayed. We provide first evidence that this unexpected phenomenon is connected to extra centrosomes eliciting a pro-death signal engaging the apoptotic machinery. Apoptosis induction requires the PIDDosome multi-protein complex, as it can be abrogated by loss of any of its three components, Caspase-2 , Raidd/Cradd , or Pidd1 . BCL2 overexpression equally blocks cell death, documenting for the first time induction of mitochondrial apoptosis downstream of extra centrosomes. Our findings demonstrate context-dependent effects of centrosome amplification during transformation and ask to adjust current belief that extra centrosomes are intrinsically pro-tumorigenic.
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معلومات مُعتمدة: DOC 82 Austria FWF_ Austrian Science Fund FWF
تواريخ الأحداث: Date Created: 20240329 Date Completed: 20240401 Latest Revision: 20240501
رمز التحديث: 20240501
مُعرف محوري في PubMed: PMC10980279
DOI: 10.1126/sciadv.adk0564
PMID: 38552015
قاعدة البيانات: MEDLINE
الوصف
تدمد:2375-2548
DOI:10.1126/sciadv.adk0564