PXD082898-1

PXD082898 is an original dataset announced via ProteomeXchange.

Title	ROCK1 restrains STING pathway activation through promoting ATR-mediated DNA damage repair in prostate cancer
Description	The stimulator of interferon genes (STING) pathway is a central regulator of antitumor immunity, yet its activation in prostate cancer remains limited. Here, through kinome-focused CRISPR screening and p-STING-based flow sorting, we identify ROCK1 as a repressor of STING signaling in prostate cancer cells. In vitro and in vivo experiments show that ROCK1 knockdown or ROCK inhibitor treatment significantly upregulates p-STING and downstream STING pathway genes. Phosphoproteomic analysis reveals decreased phosphorylation of ATR and other core DNA damage repair proteins upon ROCK1 knockdown, accompanied by elevated DNA damage marker expression. Mechanistically, co-immunoprecipitation and immunofluorescence assays demonstrate that ROCK1 knockdown markedly attenuates the binding between ATR/ATRIP and RPA32, as well as their nuclear co-localization. Rescue experiments further show that re-expression of full-length ROCK1 or its N-terminal domain restores ATRIP-RPA32 binding and ATR phosphorylation, whereas the C-terminal domain does not. Additionally, hypoxia treatment increases ROCK1 acetylation at K974, promotes ROCK1 binding to Rho proteins and enhances ATR phosphorylation. In mouse models, ROCK1 loss induces antitumor immune responses and sensitizes tumors to anti-PD-1 therapy. Clinically, elevated ROCK1 expression in human prostate cancer specimens correlates with worse prognosis and diminished CD8+ T cell infiltration. In a pilot clinical expansion, the clinically approved ROCK inhibitor fasudil combined with tislelizumab induced biochemical and radiographic responses in heavily pretreated metastatic prostate cancer patients, indicating ROCK1 blockade as a readily translatable strategy to sensitize prostate cancer to immunotherapy.
HostingRepository	iProX
AnnounceDate	2026-08-18
AnnouncementXML	Submission_2026-08-20_07:10:29.501.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiange Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-20 07:10:04	ID requested
⏵ 1	2026-08-20 07:10:30	announced

Dataset with its publication pending

submitter keyword: Prostate cancer, STING, CRISPR screening, DNA damage repair

Bin Xu
contact affiliation	Southeast University
contact email	njxbseu@seu.edu.cn
lab head
Tiange Wu
contact affiliation	Southeast University
contact email	13814032476@163.com
dataset submitter

iProX dataset URI