Evidence map›Paper›PMID 40260915›Full record

ArticleJCI insight2025

SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer.

Hui Zhang, Lili Kong, Jinhui Li, Zhihan Liu, Yiting Zhao, Xiuyi Lv, Liangpei Wu, Lin Chai, Hongjie You, Jiabei Jin and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026
    Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Hui ZhangDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Lili KongDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Jinhui LiDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Zhihan LiuDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Yiting ZhaoDepartment of Ultrasound Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
Xiuyi LvDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Liangpei WuDepartment of Ultrasound Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
Lin ChaiDepartment of Ultrasound Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
Hongjie YouDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Jiabei JinDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Xinyi CaoDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Zhong ZhengDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Yadong LiuDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Zejun YanDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Xiaofeng JinDepartment of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is well documented that impaired DNA damage repair (DDR) induces genomic instability that can efficiently increase the sensitivity of prostate cancer (PCa) cells to PARP inhibitors; however, the underlying mechanism remains elusive. Here, we found profound genomic instability in PCa cells with SPOP gene mutations and confirmed the sensitivity of SPOP-mutated PCa cells to olaparib-induced apoptosis. Mechanistically, we identified olaparib-induced CK2-mediated phosphorylation of PIAS1-S468, which in turn mediated SUMOylation of SPOP, thus promoting its E3 ligase activity in the DDR. Moreover, an abnormal CK2/PIAS1/SPOP axis due to SPOP mutations or defects in CK2-mediated phosphorylation of PIAS1, as well as SPOP inhibitor treatment, led to impaired DDR, thus increasing olaparib-induced apoptosis of PCa cells and enhancing olaparib sensitivity in animal models and patient-derived organoids. This suggested that disruption of the CK2/PIAS1/SPOP signaling axis could serve as an indicator for targeted therapy of PCa using a PARP inhibitor.

Indexed as

Casein Kinase IINuclear ProteinsPoly(ADP-ribose) Polymerase InhibitorsProstatic NeoplasmsProtein Inhibitors of Activated STATRepressor ProteinsAnimalsApoptosisCell Line, TumorDNA RepairDrug Resistance, NeoplasmGenomic InstabilityHumansMaleMiceMutationCasein Kinase IINuclear ProteinsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein Inhibitors of Activated STATRepressor ProteinsSPOP protein, humanCell biologyDNA repairDrug therapyGeneticsOncologyProstate cancer

Identifiers

PMID40260915
PMCPMC12016936

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.