PXD025600

PXD025600 is an original dataset announced via ProteomeXchange.

Title	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is upregulated in breast epithelial-mesenchymal transition and involved in oxidative stress regulation.
Description	Epithelial-mesenchymal transition (EMT) is a diverse and dynamic biological process which is involved in cancer progression. It is important for carcinoma cells during invasion and metastasis. EMT has been in the spotlight for cancer cells to disseminate to distant organs by gaining partial EMT phenotype. Cancer cells with partial EMT are believed to be more cancerogenic/invasive than cells that have undergone complete EMT. The proteomic changes that occur following EMT in breast epithelial cells and how these relate to changes in cellular metabolism are incompletely understood. To study metabolic reprogramming in different mesenchymal states, we analyzed proteomic changes following EMT in the breast epithelial cell model D492, with single-shot LFQ supported by SILAC proteomic approach. The D492 EMT cell model contains three isogenic cell lines: epithelial D492 cells, mesenchymal D492M cells, and partial mesenchymal, HER2 overexpressing, tumorigenic D492HER2 cells. Proteomic analysis positioned the D492 and D492M cells as basal-like while D492HER2 as claudin-low. Further comparison of the non-tumorigenic D492 and D492M cells to tumorigenic D492HER2 differentiated the metabolic EMT markers of migration from those of invasion. Among these were markers of glycan metabolism. We identified glutamine-fructose-6-phosphate transaminase [isomerizing] 2 (GFPT2) as the top dysregulated enzyme in glycan metabolism and found increased GFPT2 expression was a characteristic of claudin-low breast cancer. siRNA knockdown of GFPT2 influenced both cell growth and invasion in vitro and was accompanied by lowered flux through the hexosamine biosynthesis pathway (HBP). Knockdown of GFPT2 decreased cystathionine and sulfide:quinone oxidoreductase (SQOR) in the transsulfuration pathway which regulates H2S production and mitochondrial homeostasis. Moreover, GFPT2 expression was regulated by the level of reduced glutathione (GSH) and suppressed by the oxidative stress regulator, GSK3-β. Our results demonstrate that GFPT2 is a marker for oxidative stress. It is upregulated and controls growth and invasion in the D492 EMT model and is associated with claudin-low and poor prognosis in breast cancer.
HostingRepository	PRIDE
AnnounceDate	2022-01-05
AnnouncementXML	Submission_2022-01-10_13:42:40.550.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qiong Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-23 09:09:20	ID requested
1	2022-01-05 08:43:04	announced
⏵ 2	2022-01-10 13:42:41	announced	2022-01-10: Updated publication reference for PubMed record(s): 34923141.

Wang Q, Karvelsson ST, Kotronoulas A, Gudjonsson T, Halldorsson S, Rolfsson O, Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) Is Upregulated in Breast Epithelial-Mesenchymal Transition and Responds to Oxidative Stress. Mol Cell Proteomics, 21(2):100185(2022) [pubmed]

submitter keyword: Proteomics, EMT, metabolism, GFPT2, oxidative stress, claudin-low, breast cancer

Óttar Rolfsson
contact affiliation	Department of Biochemistry and Molecular Biology & The Center for Systems Biology University of Iceland Sturlugata 8, 101 Reykjavik Iceland.
contact email	ottarr@hi.is
lab head
Qiong Wang
contact affiliation	University of Iceland
contact email	qiw1@hi.is
dataset submitter

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/2022/01/PXD025600

PRIDE project URI

• PRIDE
  1. PXD025600
     1. Label: PRIDE project
     2. Name: Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is upregulated in breast epithelial-mesenchymal transition and involved in oxidative stress regulation.