PXD007890

PXD007890 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biomedical

submitter keyword: Human, pancreatic cancer, LC-MSMS

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

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/2018/01/PXD007890

PRIDE project URI

• PRIDE
  1. PXD007890
     1. Label: PRIDE project
     2. Name: Human pancreatic cancer LC-MSMS