PXD007280

PXD007280 is an original dataset announced via ProteomeXchange.

Title	Proteome analysis of hypoxic glioblastoma cells reveals sequential metabolic adaptation of one-carbon metabolic pathways
Description	Rapidly proliferating tumors are exposed to a hypoxic microenvironment due to their density, high metabolic consumption, and interruptions in blood flow due to immature angiogenesis. Cellular responses to hypoxia promote highly malignant and metastatic behavior, as well as a chemotherapy-resistant state. In order to better understand the complex relationships between hypoxic adaptations and cancer progression, we studied the dynamic proteome responses of glioblastoma cells exposed to hypoxia via an innovative approach: quantification of newly synthesized proteins using heavy stable-isotope arginine labeling combined with accurate assessment of cell replication by quantification of the light/heavy arginine ratio of peptides in histone H4. We found that hypoxia affects cancer cells in multiple intertwined ways: inflammation, typically with over-expressed glucose transporter (GLUT1), DUSP4/ MKP2, and RelA proteins; a metabolic adaptation with overexpression of all glycolytic pathway enzymes for pyruvate/lactate synthesis; and the EMT (epithelial-mesenchymal transition) and cancer stem cell (CSC) renewal with characteristic morphological changes and mesenchymal/CSC protein expression profiles. For the first time, we identified the vitamin B12 transporter protein TCN2, which is essential for one-carbon metabolism, as being significantly downregulated. Further, we found, by knockdown and overexpression experiments, that TCN2 plays an important role in controlling cancer cell transformation towards the highly aggressive mesenchymal/CSC stage; low expression of TCN2 has an effect similar to hypoxia, while high expression of TCN2 can reverse it. We conclude that hypoxia induces sequential metabolic responses of one-carbon metabolism in tumor cells.
HostingRepository	PRIDE
AnnounceDate	2017-09-07
AnnouncementXML	Submission_2017-09-07_01:41:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kangling Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-16 02:01:03	ID requested
⏵ 1	2017-09-07 01:41:32	announced

Zhang K, Xu P, Sowers JL, Machuca DF, Mirfattah B, Herring J, Tang H, Chen Y, Tian B, Brasier AR, Sowers LC, Proteome Analysis of Hypoxic Glioblastoma Cells Reveals Sequential Metabolic Adaptation of One-Carbon Metabolic Pathways. Mol Cell Proteomics, 16(11):1906-1921(2017) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biological, Biomedical

submitter keyword: Hypoxia, one carbon, protein pathways, proteomics

Kangling Zhang
contact affiliation	University of Texas Medical Branch
contact email	kazhang@utmb.edu
lab head
Kangling Zhang
contact affiliation	University of Texas Medical Branch
contact email	kazhang@utmb.edu
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/2017/09/PXD007280

PRIDE project URI

• PRIDE
  1. PXD007280
     1. Label: PRIDE project
     2. Name: Proteome analysis of hypoxic glioblastoma cells reveals sequential metabolic adaptation of one-carbon metabolic pathways