PXD023142 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Serine biosynthesis is a metabolic vulnerability in IDH2-driven breast cancer progression |
Description | Cancer-specific metabolic phenotypes and their vulnerabilities are one among the viable areas of cancer research. We studied the association of breast cancer subtypes with different metabolic phenotypes and identified isocitrate dehydrogenase 2 (IDH2) as a key player in triple negative breast cancer (TNBC) and HER2. Functional assays combined with mass spectrometry-based analyses reveal the oncogenic role of IDH2 in cell proliferation, anchorage-independent growth, glycolysis, mitochondrial respiration and antioxidant defense. Genome-scale metabolic modeling identified PHGDH and PSAT1 as the synthetic dosage lethal (SDL) partners of IDH2. In agreement, CRISPR-Cas9 knockout of PHGDH and PSAT1 showed the essentiality of serine biosynthesis proteins in IDH2-high cells. The clinical significance of the SDL interaction showed patients with IDH2-high/PHGDH-low have better survival than IDH2-high/PHGDH-high. Furthermore, we show the efficacy of PHGDH inhibitors in treating IDH2-high cells in vitro and in in vivo. Altogether, our study creates a new link between two known cancer regulators and emphasizes PHGDH as a promising target for TNBC with IDH2 overexpression. |
HostingRepository | PRIDE |
AnnounceDate | 2021-01-04 |
AnnouncementXML | Submission_2021-01-04_07:18:06.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tamar Geiger |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-12-15 04:18:25 | ID requested | |
⏵ 1 | 2021-01-04 07:18:06 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: breast cancer / isocitrate dehydrogenase 2 / mass spectrometry / metabolic vulnerability /serine biosynthesis |
Contact List
Tamar Geiger |
contact affiliation | Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel |
contact email | geiger@tauex.tau.ac.il |
lab head | |
Tamar Geiger |
contact affiliation | Tel Aviv University |
contact email | geiger@tauex.tau.ac.il |
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/2021/01/PXD023142 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD023142
- Label: PRIDE project
- Name: Serine biosynthesis is a metabolic vulnerability in IDH2-driven breast cancer progression