PXD002394 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic and phosphoproteomic analysis of cisplatin resistance in patient derived serous ovarian cancer |
Description | Understanding the mechanism of resistance in platinum-based regimens for the treatment of high-grade serous ovarian cancer (HGSOC) is important for identifying new therapeutic targets to improve the clinical outcome of ovarian cancer patients. Mass spectrometry-based proteomic strategy was applied to spheroidal cisplatin sensitive and resistant HGSOC generated cell lines in the absence and presence of cisplatin drug. A complete expressed HGSOC proteome and phosphoproteome was characterized in cisplatin sensitive and resistant HGSOC cell lines providing insight into the mechanism of resistance development. PCA analysis showed that phosphorylation of a few proteins provides better classification than the whole proteome of the cellular subtypes. Specifically, a distinctive phosphoproteomic signature between cisplatin sensitive and resistant cell lines in the absence of drug was observed. This same phosphoproteomic signature was observed in our cisplatin sensitive cell line in the absence and presence of drug, indicating a vital role for phosphorylation of proteins in resistance development to cisplatin. The most phosphorylated protein was sequestosome (p62/SQSTM1). Differential expressions of apoptosis by the prognostic factor ratio of Bcl-2/Bax and autophagy, known to be regulated by p62/SQSTM1, was validated in the proteome data and by western blot analysis. A significant increase in apoptosis in the presence of cisplatin was observed in only the sensitive cell line while autophagy revealed increased expression in the resistant relative to sensitive cell line. Furthermore, site specific phosphorylation on 20 modified residues of sequestosome was characterized. Elevated expression of phosphorylation of sequestosome in resistant HGSOC cell lines was validated with western blot analysis. Here, we propose phosphorylation of sequestosome to be a marker and key in cisplatin resistance development in HGOSC ovarian cancers by shuttling ubiquitinated proteins to the autophagy pathway and influencing down-regulation of apoptosis. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:11:40.103.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Elizabeth Nguyen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-06-18 06:06:47 | ID requested | |
1 | 2017-05-02 05:08:59 | announced | |
⏵ 2 | 2024-10-22 04:11:42 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1074/mcp.M116.058321; |
Nguyen EV, Huhtinen K, Goo YA, Kaipio K, Andersson N, Rantanen V, Hynninen J, Lahesmaa R, Carpen O, Goodlett DR, Hyper-phosphorylation of Sequestosome-1 Distinguishes Resistance to Cisplatin in Patient Derived High Grade Serous Ovarian Cancer Cells. Mol Cell Proteomics, 16(7):1377-1392(2017) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: phosphoproteomic, resistance, ovarian cancer, cisplatin,MS/MS |
Contact List
Dr. David Goodlett |
contact affiliation | Department of Pharmaceutical Sciences University of Maryland Baltimore, Maryland USA |
contact email | dgoodlett@rx.umaryland.edu |
lab head | |
Elizabeth Nguyen |
contact affiliation | Post-doctoral scientist |
contact email | minguyen@btk.fi |
dataset submitter | |
Full Dataset Link List
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/2017/05/PXD002394 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002394
- Label: PRIDE project
- Name: Proteomic and phosphoproteomic analysis of cisplatin resistance in patient derived serous ovarian cancer