PXD022908

PXD022908 is an original dataset announced via ProteomeXchange.

Title	Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines
Description	Small-molecule tankyrase 1 and tankyrase 2 (TNKS1/2) inhibitors are effective anti-tumor agents in selected tumor cell lines and mouse models. Here, we characterized the response signatures and the in-depth mechanisms for the anti-proliferative 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 in particular 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 WNT/β-catenin, YAP and PI3K/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-catenin degradasomes functioning as central complexes interacting with YAP and AMOT proteins during attenuation of YAP signaling. These findings provide a contextual and mechanistic framework for using TNKSi in anti-cancer treatment that warrants further comprehensive preclinical and clinical evaluations.
HostingRepository	PRIDE
AnnounceDate	2021-11-03
AnnouncementXML	Submission_2021-11-08_05:30:14.930.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin Strand
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deaminated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-04 03:03:20	ID requested
1	2021-11-03 07:36:01	announced
⏵ 2	2021-11-08 05:30:15	announced	2021-11-08: Updated publication reference for PubMed record(s): 34337362.

Mygland L, Brinch SA, Strand MF, Olsen PA, Aizenshtadt A, Lund K, Solberg NT, Lycke M, Thorvaldsen TE, Espada S, Misaghian D, Page CM, Agafonov O, Nyg, å, rd S, Chi NW, Lin E, Tan J, Yu Y, Costa M, Krauss S, Waaler J, Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines. iScience, 24(7):102807(2021) [pubmed]

submitter keyword: SILAC, Cancer, Tankyrase,

Jo Waaler
contact affiliation	Department of Immunology and Transfusion Medicine, Oslo University Hospital and Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo. P.O. Box 1110 Blindern 0317, Oslo, Norway.
contact email	jo.waaler@rr-research.no
lab head
Martin Strand
contact affiliation	Kristiania University College, School of Health Sciences
contact email	martinfrank.strand@kristiania.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022908
     1. Label: PRIDE project
     2. Name: Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines