PXD007890
PXD007890 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Human pancreatic cancer LC-MSMS |
Description | Despite decades of effort, pancreatic adenocarcinoma (PDAC) remains an intractable clinical challenge. An insufficient understanding of mechanisms underlying tumor cell responses to chemotherapy contributes significantly to the lack of effective treatment regimens. Here, paclitaxel, a first-line chemotherapeutic agent, was observed to interact synergistically with birinapant, a Second Mitochondrial-derived Activator of Caspases mimetic. Therefore, we investigated molecular-level drug interaction mechanisms using comprehensive, reproducible, and well-controlled ion-current-based MS1 quantification (IonStar). In a set of 40 biological samples, we compared temporal proteomic responses of PDAC cells treated with birinapant and paclitaxel, alone and combined. Using stringent criteria (e.g. strict false-discovery-rate FDR control, 2 peptides/protein), we quantified 4069 unique proteins confidently (99.8% without any missing data), and 541 proteins were significantly altered in the three treatment groups with a FDR of <1%. Interestingly, most of these proteins were altered only by combined birinapant/paclitaxel, and these predominantly represented three biological processes: mitochondrial function, cell growth and apoptosis, and cell cycle arrest. Proteins responsible for activation of oxidative phosphorylation, fatty acid β-oxidation, and inactivation of aerobic glycolysis were altered largely by combined birinapant/paclitaxel compared to single drugs, suggesting that the Warburg effect, which is employed by PDAC cells for survival and proliferation, was alleviated by the combination treatment. Metabolic profiling confirmed substantially greater suppression of the Warburg effect by the combined agents compared to either drug alone. Western blot analysis confirmed changes in apoptosis/survival signaling pathways, such as inhibition of PI3K/AKT, JAK/STAT, and MAPK/ERK signal transduction, as well as induction of G2/M arrest, and the drug combination induced much more apoptosis than did single agents. Overall, this in-depth, large-scale proteomics study provided novel insights into molecular mechanisms underlying synergy of combined birinapant/paclitaxel, and describes a proteomics/informatics pipeline that can be applied broadly to the development of cancer drug combination regimens. |
HostingRepository | PRIDE |
AnnounceDate | 2020-10-27 |
AnnouncementXML | Submission_2020-10-27_08:01:19.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD007890 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | xue wang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Oxidation; Acetyl; Carbamidomethyl |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2017-10-02 07:43:25 | ID requested | |
1 | 2018-01-29 10:19:21 | announced | |
⏵ 2 | 2020-10-27 08:01:21 | announced | 2020-10-27: Updated publication reference for PubMed record(s): 29358341, 33097020. |
Publication List
Wang X, Niu J, Li J, Shen X, Shen S, Straubinger RM, Qu J, Large-Scale, Ion-Current-Based Quantitative Proteomics (IonStar). Mol Cell Proteomics, 17(4):655-671(2018) [pubmed] |
Niu J, Wang X, Qu J, Mager DE, Straubinger RM, in pancreatic cancer cells. BMC Cancer, 20(1):1024(2020) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human, pancreatic cancer, LC-MSMS |
Contact List
Jun Qu | |
---|---|
contact affiliation | University at buffalo |
contact email | junqu@buffalo.edu |
lab head | |
xue wang | |
contact affiliation | University at buffalo |
contact email | xwang79@buffalo.edu |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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