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PXD036826

PXD036826 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDeep Phosphoproteomic Elucidation of Metformin-Signaling in Heterogenous Colorectal Cancer Cells
DescriptionThe biguanide drug metformin is a safe and widely prescribed drug for type 2 diabetes. Interestingly, hundreds of clinical trials were set to evaluate the potential role of metformin in the prevention and treatment of cancer including colorectal cancer (CRC). However, the metformin-induced cell signaling remains controversial. To interrogate cell signaling events and networks in CRC and explore the druggability of the metformin-rewired phosphorylation network, we performed a proteomic and phosphoproteomic analysis on a panel of 12 molecularly heterogeneous CRC cell lines. Using in-depth data-independent analysis mass spectrometry (DIA-MS), we profiled a total of 10,142 proteins and 56,080 phosphosites (P-sites) in CRC cells treated with metformin for 30 minutes and 24 hours. Our results indicate that metformin tends to not trigger or inhibit significant immediate phosphorylation events. Instead, it primarily remodels cell signaling in the long-term. Strikingly, the phosphorylation response to metformin was highly heterogeneous in the CRC panel. We further performed a network analysis to systematically estimate kinase/phosphatase activities and reconstruct signaling cascades in each cell line. We created a “MetScore” which catalogs the most consistently perturbed P-sites among CRC cells for future studies. Finally, we leveraged the metformin P-site signature to identify pharmacodynamic interactions, revealing and confirming a number of candidate metformin-interacting drugs, including navitoclax, a BCL-2/BCL-xL inhibitor. Together, we provide a state-of-the-art phosphoproteomic resource to explore the metformin-induced cell signaling for potential cancer therapeutics.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:27:13.774.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYansheng Liu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-17 15:13:47ID requested
12023-02-18 15:15:08announced
22023-11-14 08:27:15announced2023-11-14: Updated project metadata.
Publication List
Salovska B, Gao E, M, ü, ller-Dott S, Li W, Cordon CC, Wang S, Dugourd A, Rosenberger G, Saez-Rodriguez J, Liu Y, Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities. Clin Transl Med, 13(2):e1179(2023) [pubmed]
Keyword List
submitter keyword: DIA-MS, phosphoproteomics, metformin, colorectal cancer
Contact List
Yansheng Liu
contact affiliationYale Cancer Biology Institute, Department of Pharmacology, Yale University School of Medicine
contact emailyansheng.liu@yale.edu
lab head
Yansheng Liu
contact affiliationYale University School of Medicine
contact emailyansheng.liu@yale.edu
dataset submitter
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Dataset FTP location
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