Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines.

Cancer Proteomics Transcriptomics

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
23 Jul 2021
Historique:
received: 09 02 2021
revised: 26 05 2021
accepted: 28 06 2021
entrez: 2 8 2021
pubmed: 3 8 2021
medline: 3 8 2021
Statut: epublish

Résumé

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/β-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 β

Identifiants

pubmed: 34337362
doi: 10.1016/j.isci.2021.102807
pii: S2589-0042(21)00775-6
pmc: PMC8313754
doi:

Types de publication

Journal Article

Langues

eng

Pagination

102807

Informations de copyright

© 2021 The Authors.

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Auteurs

Line Mygland (L)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Shoshy Alam Brinch (SA)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Martin Frank Strand (MF)

School of Health Sciences, Kristiania University College, P.O. Box 1190 Sentrum, 0107 Oslo, Norway.

Petter Angell Olsen (PA)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Aleksandra Aizenshtadt (A)

Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Kaja Lund (K)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.

Nina Therese Solberg (NT)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.

Max Lycke (M)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.

Tor Espen Thorvaldsen (TE)

Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway.

Sandra Espada (S)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Dorna Misaghian (D)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.

Christian M Page (CM)

Center for Fertility and Health, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, 0213 Oslo, Norway.
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway.

Oleg Agafonov (O)

Bioinformatics Core Facility, Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital, Ullernchausseen 70, 0379 Oslo, Norway.

Ståle Nygård (S)

Department of Informatics, University of Oslo, P.O. box 080 Blindern, 0316 Oslo, Norway.

Nai-Wen Chi (NW)

Endocrine Service, VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.

Eva Lin (E)

Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Jenille Tan (J)

Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Yihong Yu (Y)

Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Mike Costa (M)

Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Stefan Krauss (S)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Jo Waaler (J)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.

Classifications MeSH