دورية أكاديمية
أعرض في EDS

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer.

التفاصيل البيبلوغرافية
العنوان: The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer.
المؤلفون: Patterson MR; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK. molly.patterson@pennmedicine.upenn.edu.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK. molly.patterson@pennmedicine.upenn.edu., Cogan JA; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK., Cassidy R; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK., Theobald DA; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK., Wang M; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK., Scarth JA; Barts Cancer Institute, Queen Mary University of London, London, UK., Anene CA; Barts Cancer Institute, Queen Mary University of London, London, UK.; Centre for Biomedical Science Research, Leeds Beckett University, Leeds, UK., Whitehouse A; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK., Morgan EL; School of Life Sciences, University of Sussex, Brighton, UK., Macdonald A; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK. a.macdonald@leeds.ac.uk.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK. a.macdonald@leeds.ac.uk.
المصدر: Nature communications [Nat Commun] 2024 Jul 10; Vol. 15 (1), pp. 5809. Date of Electronic Publication: 2024 Jul 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Adaptor Proteins, Signal Transducing*/metabolism , Adaptor Proteins, Signal Transducing*/genetics , Cell Proliferation* , Hippo Signaling Pathway* , Human papillomavirus 18*/genetics , Human papillomavirus 18*/metabolism , Papillomavirus Infections*/virology , Papillomavirus Infections*/metabolism , Papillomavirus Infections*/genetics , Papillomavirus Infections*/pathology , Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Signal Transduction* , Transcription Factors*/metabolism , Transcription Factors*/genetics , Uterine Cervical Neoplasms*/virology , Uterine Cervical Neoplasms*/metabolism , Uterine Cervical Neoplasms*/genetics , Uterine Cervical Neoplasms*/pathology , YAP-Signaling Proteins*/metabolism, Female ; Humans ; Carcinogenesis/genetics ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16/genetics ; Human papillomavirus 16/metabolism ; Trans-Activators/metabolism ; Trans-Activators/genetics ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism
مستخلص: Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers.
(© 2024. The Author(s).)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MR/X009564/1 RCUK | Medical Research Council (MRC); MR/W006944/1 RCUK | Medical Research Council (MRC); BB/T007222/1 RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
0 (Trans-Activators)
0 (Transcription Factors)
0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
0 (WWTR1 protein, human)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)
تواريخ الأحداث: Date Created: 20240710 Date Completed: 20240710 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11237029
DOI: 10.1038/s41467-024-49965-9
PMID: 38987584
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-49965-9