PXD068325 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-09-12 08:38:47 | ID requested | |
| ⏵ 1 | 2026-03-23 10:11:19 | announced | |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: glioma stem cell,glioblastoma, proline, ROS |
Contact List
| 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 | |
Full Dataset Link List
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 |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD068325
- Label: PRIDE project
- Name: Cancer Stem Cells Induce Proline Synthesis through FAM3C-Mediated SPIN1 Stabilization to Attenuate ROS Stress
