PXD036826 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Deep Phosphoproteomic Elucidation of Metformin-Signaling in Heterogenous Colorectal Cancer Cells |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:27:13.774.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yansheng Liu |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-17 15:13:47 | ID requested | |
1 | 2023-02-18 15:15:08 | announced | |
⏵ 2 | 2023-11-14 08:27:15 | announced | 2023-11-14: 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 affiliation | Yale Cancer Biology Institute, Department of Pharmacology, Yale University School of Medicine |
contact email | yansheng.liu@yale.edu |
lab head | |
Yansheng Liu |
contact affiliation | Yale University School of Medicine |
contact email | yansheng.liu@yale.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036826
- Label: PRIDE project
- Name: Deep Phosphoproteomic Elucidation of Metformin-Signaling in Heterogenous Colorectal Cancer Cells