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PXD023142

PXD023142 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSerine biosynthesis is a metabolic vulnerability in IDH2-driven breast cancer progression
DescriptionCancer-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.
HostingRepositoryPRIDE
AnnounceDate2021-01-04
AnnouncementXMLSubmission_2021-01-04_07:18:06.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTamar Geiger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-12-15 04:18:25ID requested
12021-01-04 07:18:06announced
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 affiliationDepartment of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel
contact emailgeiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliationTel Aviv University
contact emailgeiger@tauex.tau.ac.il
dataset submitter
Full Dataset Link List
Dataset FTP location
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