PXD023142-1

PXD023142 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-15 04:18:25	ID requested
⏵ 1	2021-01-04 07:18:06	announced

Dataset with its publication pending

submitter keyword: breast cancer / isocitrate dehydrogenase 2 / mass spectrometry / metabolic vulnerability /serine biosynthesis

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

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PRIDE project URI

• PRIDE
  1. PXD023142
     1. Label: PRIDE project
     2. Name: Serine biosynthesis is a metabolic vulnerability in IDH2-driven breast cancer progression