PXD068325

PXD068325 is an original dataset announced via ProteomeXchange.

Title	Cancer Stem Cells Induce Proline Synthesis through FAM3C-Mediated SPIN1 Stabilization to Attenuate ROS Stress
Description	Tumors reprogram amino acid metabolism to dysregulate cellular growth through multiple mechanisms. Here, we find that glioblastoma (GBM) stem cells (GSCs) contain increased proline levels relative to differentiated GBM cells (DGCs) through increased proline synthesis. We identified FAM3C (FAM3 Metabolism Regulating Signaling Molecule C) as an upstream driver of proline synthetic enzyme expression. The core stem cell transcription factor, SOX2, drove GSC-specific expression of FAM3C. FAM3C is secreted, but, in GSCs, intracellular FAM3C directly bound histone 3 lysine 4 trimethyl lysine 9 trimethyl (H3K4me3K9me3) reader, SPIN1 (Spindlin1), to prevent SPIN1 lysosomal degradation and promote epigenetic regulation of proline synthesis. Proline synthesis depletes reactive oxygen species (ROS); genetic targeting of FAM3C attenuated ROS scavenging, while SPIN1 overexpression restored ROS levels. Molecular docking screening identified tucatinib as a brain penetrant pharmacologic disruptor of FAM3C-SPIN1 interactions, promoting SPIN1 degradation and reducing intracellular proline levels. Thus, the SOX2-FAM3C-SPIN1 axis activates proline metabolism in GBM and targeted through repurposing of tucatinib.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-23_10:11:19.236.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weichi Wu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker TDF format

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-12 08:38:47	ID requested
⏵ 1	2026-03-23 10:11:19	announced

Dataset with its publication pending

submitter keyword: glioma stem cell,glioblastoma, proline, ROS

Jeremy N.
contact affiliation	1. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA 2. UPMC Hillman Cancer Center, Pittsburgh, PA, USA 3. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA 4. Department of Neurology, University of North Carolina, Chapel Hill, NC, USA
contact email	drjeremyrich@gmail.com
lab head
Weichi Wu
contact affiliation	Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
contact email	wuweichi@hotmail.com
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/2026/03/PXD068325

PRIDE project URI

• PRIDE
  1. PXD068325
     1. Label: PRIDE project
     2. Name: Cancer Stem Cells Induce Proline Synthesis through FAM3C-Mediated SPIN1 Stabilization to Attenuate ROS Stress