PXD080662-1

PXD080662 is an original dataset announced via ProteomeXchange.

Title	Mechanistic Insights into CDCA5-Mediated Regulation of Ferroptosis via the p53-PP2Ac-STEAP3 Axis: Impacts on Iron Uptake and Tumor Growth
Description	Background:Cell cycle dysregulation is a hallmark of tumorigenesis. While Cell Division Cycle-Associated 5 (CDCA5,or Sororin) is known to govern chromosome cohesion and mitotic exit, its specific role in hepatocellular carcinoma (HCC) progression and immunometabolic regulation remains elusive. Methods:Transcriptomic sequencing of clinical HCC samples and analysis of The Cancer Genome Atlas (TCGA) and Genome-Tissue Expression database revealed that CDCA5 is upregulated in HCC and associated with poor prognosis.Multiple bioinformatics analyses showed that CDCA5 expression correlates with immune infiltration, DNA repair, genomic instability, and tumor microenvironment (TME) scores across various cancer types.We then demonstrated the effects of CDCA5 on HCC cells using both in vitro and in vivo experiments, such as CCK-8, EdU, colony formation, Transwell, wound-healing assays, and flow cytometry to analyze the cell cycle and apoptosis.Furthermore, the negative regulation of ferroptosis by CDCA5 was identified via the p53-PP2Ac-STEAP3 axis using proteomic analysis, ChIP-qPCR, and dual-luciferase reporter assaysCDCA5's effects on ferroptosis were evaluated by quantifying levels of MDA, ROS, and GSH, along with mitochondrial activity and iron ions. These findings were validated using ferroptosis inhibitors and activators. Results:Pan-cancer analysis identified CDCA5 as a robust diagnostic and prognostic biomarker, significantly correlating with genomic instability, DNA mutation burden, and distinct immune infiltration patterns across malignancies. In HCC, CDCA5 knockdown markedly suppressed proliferation and migration while inducing ferroptosis.We elucidated a fresh signaling pathway where CDCA5 downregulates PP2Ac, ensuring the phosphorylation of p53.Hyperphosphorylated p53 acts to repress STEAP3 transcription, thereby reducing iron uptake and blocking ferroptosis, which supports tumor growth. Conclusions: This investigation reveals a new CDCA5/PP2Ac/p53/STEAP3 mechanism that links cell cycle misregulation to the escape from ferroptosis. CDCA5 is identified as an important biomarker across various cancers for immune infiltration and a potential therapeutic target for HCC, providing new approaches to trigger ferroptosis in tumors.
HostingRepository	iProX
AnnounceDate	2026-07-07
AnnouncementXML	Submission_2026-07-07_01:31:18.737.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gang Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-07 01:30:58	ID requested
⏵ 1	2026-07-07 01:31:19	announced

Dataset with its publication pending

submitter keyword: Pan-cancer analysis, Genome instability, Immunoinfiltration, ferroptosis, CDCA5, p53

Gang Wu
contact affiliation	First Hospital of China Medical University
contact email	cmuwgzwl@126.com
lab head
Gang Wu
contact affiliation	First Hospital of China Medical University
contact email	cmuwgzwl@126.com
dataset submitter

iProX dataset URI