PXD009666

PXD009666 is an original dataset announced via ProteomeXchange.

Title	Proteomic response of diffuse midline glioma to HDAC inhibition reveals adjuvant anti-EBP50 therapy as novel therapeutic concept.
Description	Diffuse midline glioma (DMG) is an aggressive pediatric tumor localized in the brainstem. The median survival after diagnosis is less than one year. Surgical resection is not possible due to the critical localization of the tumor and radiation therapy alone or in combination with chemotherapy show only minimal benefit. In 80% of cases, DIPGs are harbor genetic abnormalities such as a K27M mutation in histone H3, suggesting drugs targeting epigenetic anomalies might be efficient. Indeed, Grasso et al. (Nature Medicine, 2015) have shown that the histone deacetylase inhibitor panobinostat (PS) affects glioma cell growth in vitro and in vivo. PS is currently undergoing phase 1 clinical trials. To better understand the mechanism of action of PS on tumor cells, we performed a proteomic analysis by comparing DMG cells treated with panobinostat to control cells. We identified 2 proteins in PS-treated cells: EBP50 (or NHERF-1) and IRSp53 (or BAIAP2). EBP50 protein is implicated in invasion (Kislin et al. Neoplasia, 2009) but it can also act like a tumor suppressor on glioblastoma (Molina et al. Cancer Research, 2010). There is a dual role of the protein which depends on its localization in the cell: when localized at the cell membrane, EBP50 acts as a tumor suppressor, but has oncogenic properties when present in the cytoplasm or nucleus. Using electron microscopy combined with immunofluorescence, we could validate expression of EBP50 in all cellular compartments. IRSp53 is implicated in proliferation of tumor cells (Liu P.S. Oncogene, 2010) and may have an important role during migration and invasion (Funato et al., Cancer Research 2004). To elucidate the role of the two proteins in DIPG, we investigated effects of gene knockdown by siRNA and stable overexpression using lentiviruses. For each protein, we found a significant diminution of proliferation, migration and invasion and an increase in apoptosis cells were transfected with siRNAs. In contrast, overexpression of EBP50 did not have any effect on cells. Our results suggest that the two proteins induced by PS treatment are implicated in tumor progression and might constitute novel additional therapeutic targets, especially as adjuvant treatment together with PS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:22:54.636.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-04 01:17:17	ID requested
1	2021-06-10 08:22:37	announced
⏵ 2	2024-10-22 05:22:56	announced	2024-10-22: Updated project metadata.

10.1093/neuonc/noz215;

Capdevielle C, Desplat A, Charpentier J, Sagliocco F, Thiebaud P, Th, é, z, é N, F, é, dou S, Hooks KB, Silvestri R, Guyonnet-Duperat V, Petrel M, Raymond AA, Dupuy JW, Grosset CF, Hagedorn M, HDAC inhibition induces expression of scaffolding proteins critical for tumor progression in pediatric glioma: focus on EBP50 and IRSp53. Neuro Oncol, 22(4):550-562(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: label-free quantitative proteome analysis., EBP50, ezrin-radixin-moesin binding protein 50, diffuse midline glioma,DMG, HDAC inhibition

Martin Hagedorn
contact affiliation	Univ Bordeaux, U1035 INSERM, France
contact email	martin.hagedorn@u-bordeaux.fr
lab head
Dupuy Jean-William
contact affiliation	Plateforme Proteome Bordeaux
contact email	jean-william.dupuy@u-bordeaux.fr
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/2021/06/PXD009666

PRIDE project URI

• PRIDE
  1. PXD009666
     1. Label: PRIDE project
     2. Name: Proteomic response of diffuse midline glioma to HDAC inhibition reveals adjuvant anti-EBP50 therapy as novel therapeutic concept.