PXD021562

PXD021562 is an original dataset announced via ProteomeXchange.

Title	Cooperative treatment effectiveness of VE821 and AUY922 in Ewing’s sarcoma cells
Description	Ewing's sarcoma (ES) is the second most frequent bone cancer during childhood and adolescence originating from a translocation between the EWSR1 and the FLI1 gene, which inactivates BRCA-mediated DNA damage response. Both ATR and HSP90 inhibitors are promising new candidates in the field of ES treatment. We show that the HSP90 inhibitor AUY922 alone induced DNA damages, apoptosis and ER stress, while reducing the abundance of DNA repair proteins. The combinations of the ATR inhibitor VE821 and AUY922 (AUY-VE) led to strong apoptosis induction in ES cell lines, originating from a common set of molecular targets and independent of their p53 status, yet based on different molecular mechanisms. P53 wild-type ES cells activated pro-apoptotic gene transcription and underwent mitochondria-mediated apoptosis. P53 null ES cells, however, accumulated higher level of DNA damage, ER stress and autophagy, finally leading to apoptosis. Moreover, AUY-VE treatment compromised ES cell vitality due to impaired PI3K/AKT/mTOR signaling. Unexpectedly, the combinations of AUY922 with the ATM inhibitor, KU55933 failed to kill ES cells and showed protective effects compared to AUY-VE. In summary, we provide mechanistic insights into the effective ES cell killing by ATR and HSP90 inhibitor combinations, which also offers a targetable approach for BRCA-deficient tumors, irrespective of their p53 status and may give rise to new therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:29:02.842.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joanna Kirkpatrick
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-18 04:47:38	ID requested
1	2021-09-09 08:06:21	announced
⏵ 2	2024-10-22 05:29:03	announced	2024-10-22: Updated project metadata.

10.1186/s13578-021-00571-y;

Marx C, Schaarschmidt MU, Kirkpatrick J, Marx-Bl, ü, mel L, Halilovic M, Westermann M, Hoelzer D, Meyer FB, Geng Y, Buder K, Schadwinkel HM, Siniuk K, Becker S, Thierbach R, Beck JF, Sonnemann J, Wang ZQ, Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing's sarcoma cells. Cell Biosci, 11(1):57(2021) [pubmed]

submitter keyword: Ewing's sarcoma

Zhao-Qi Wang
contact affiliation	Leibniz Institute on Aging Fritz Lipmann Institute (FLI) Beutenbergstr. 11 07745 Jena, Germany
contact email	zhao-qi.wang@leibniz-fli.de
lab head
Joanna Kirkpatrick
contact affiliation	The Francis Crick Institute
contact email	joanna.kirkpatrick@leibniz-fli.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD021562

PRIDE project URI

• PRIDE
  1. PXD021562
     1. Label: PRIDE project
     2. Name: Cooperative treatment effectiveness of VE821 and AUY922 in Ewing’s sarcoma cells