PXD051485

PXD051485 is an original dataset announced via ProteomeXchange.

Title	Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis
Description	PTEN plays a crucial role in preventing the development of glioblastoma (GBM), a severe and untreatable brain cancer. In GBM, most PTEN deficiencies arise from missense mutations, many of which have not been thoroughly examined. Here, we leveraged genetically modified mice and matched isogenic astrocyte cell cultures to investigate how specific and clinically relevant PTEN mutations (G36E, L42R, C105F, and R173H) behave in the development of GBM driven by EGFR. We report that the tumor-suppressive abilities of these PTEN mutants do not depend on their ability to act as lipid phosphatases but are instead related to their increased presence at the cell membrane. Moreover, these PTEN mutations led to heightened EGFR activity by keeping EGFR within endomembranes longer, affecting its signaling behavior. Through comprehensive studies on global protein phosphorylation and kinase library analyses in cells with the G36E and L42R PTEN mutations, we identified distinct cancer-promoting pathways activated by EGFR, offering new targets for treating GBM with these PTEN alterations.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_14:17:27.701.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-16 03:51:31	ID requested
⏵ 1	2025-05-06 14:17:28	announced

Jun HJ, Paulo JA, Appleman VA, Yaron-Barir TM, Johnson JL, Yeo AT, Rogers VA, Kuang S, Varma H, Gygi SP, Trotman LC, Charest A, Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis. iScience, 27(12):111278(2024) [pubmed]

10.1016/j.isci.2024.111278;

submitter keyword: Epidermal growth factor receptor (EGFR), Glioblastoma,Phosphatase and Tensin homolog (PTEN), Genetically engineered mouse model

Alain Charest
contact affiliation	Beth Israel Deaconess Medical Center, Harvard Medical School Boston MA 02215 United States
contact email	acharest@bidmc.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.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/2025/05/PXD051485

PRIDE project URI

• PRIDE
  1. PXD051485
     1. Label: PRIDE project
     2. Name: Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis