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Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines.
Mygland, Line; Brinch, Shoshy Alam; Strand, Martin Frank; Olsen, Petter Angell; Aizenshtadt, Aleksandra; Lund, Kaja; Solberg, Nina Therese; Lycke, Max; Thorvaldsen, Tor Espen; Espada, Sandra; Misaghian, Dorna; Page, Christian M; Agafonov, Oleg; Nygård, Ståle; Chi, Nai-Wen; Lin, Eva; Tan, Jenille; Yu, Yihong; Costa, Mike; Krauss, Stefan; Waaler, Jo.
Afiliación
  • Mygland L; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Brinch SA; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
  • Strand MF; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Olsen PA; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
  • Aizenshtadt A; School of Health Sciences, Kristiania University College, P.O. Box 1190 Sentrum, 0107 Oslo, Norway.
  • Lund K; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Solberg NT; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
  • Lycke M; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
  • Thorvaldsen TE; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Espada S; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Misaghian D; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Page CM; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
  • Agafonov O; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Nygård S; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
  • Chi NW; Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
  • Lin E; Center for Fertility and Health, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway.
  • Tan J; Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway.
  • Yu Y; Bioinformatics Core Facility, Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital, Ullernchausseen 70, 0379 Oslo, Norway.
  • Costa M; Department of Informatics, University of Oslo, P.O. box 080 Blindern, 0316 Oslo, Norway.
  • Krauss S; Endocrine Service, VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
  • Waaler J; Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
iScience ; 24(7): 102807, 2021 Jul 23.
Article en En | MEDLINE | ID: mdl-34337362
Small-molecule tankyrase 1 and tankyrase 2 (TNKS1/2) inhibitors are effective antitumor agents in selected tumor cell lines and mouse models. Here, we characterized the response signatures and the in-depth mechanisms for the antiproliferative effect of tankyrase inhibition (TNKSi). The TNKS1/2-specific inhibitor G007-LK was used to screen 537 human tumor cell lines and a panel of particularly TNKSi-sensitive tumor cell lines was identified. Transcriptome, proteome, and bioinformatic analyses revealed the overall TNKSi-induced response signatures in the selected panel. TNKSi-mediated inhibition of wingless-type mammary tumor virus integration site/ß-catenin, yes-associated protein 1 (YAP), and phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT signaling was validated and correlated with lost expression of the key oncogene MYC and impaired cell growth. Moreover, we show that TNKSi induces accumulation of TNKS1/2-containing ß-catenin degradasomes functioning as core complexes interacting with YAP and angiomotin proteins during attenuation of YAP signaling. These findings provide a contextual and mechanistic framework for using TNKSi in anticancer treatment that warrants further comprehensive preclinical and clinical evaluations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos