Evidence map›Paper›PMID 40662365›Full record

ArticleThe Journal of clinical investigation2025

Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.

Zixi Wang, Lei Li, Qi Ye, Yuzeshi Lei, Mingming Lu, Leihong Ye, Jialu Kang, Wenyue Huang, Shan Xu, Ke Wang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Identification ofTranslational cancer research · 2026
    Article
  2. Review
  3. Article
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.

Zixi WangDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Lei LiDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Qi YeDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Yuzeshi LeiDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Mingming LuDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Leihong YeDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Jialu KangDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Wenyue HuangDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Shan XuDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Ke WangDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Jing LiuDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Yang GaoDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Chenji WangState Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, China.
Jian MaDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Lei LiDepartment of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nuclear size is crucial for cellular functions and often increases with malignancy. Irregular nuclei are linked to aggressive tumors, driven by genetic and epigenetic changes. However, the precise mechanisms controlling nuclear size are still not fully understood. In this study, we demonstrated that cancer-associated speckle-type POZ protein (SPOP) mutations enlarged nuclear size by reducing the protein level of lamin B2 (LMNB2), a key nuclear integrity protein. Mechanistically, SPOP bound to LMNB2 and promoted its mono-ubiquitination at lysine-484, which protected it from degradation by the E3 ubiquitin ligase WD repeat domain 26. SPOP mutations disrupted this process, leading to reduced LMNB2 levels and impaired nuclear envelope (NE) integrity. This compromised NE was more vulnerable to damage from farnesyltransferase inhibitors (FTIs), causing nuclear rupture in SPOP-mutant tumor cells. This study identified SPOP as a positive regulator of nuclear size; the findings suggest tumors with SPOP mutations may be vulnerable to FTI-based therapies.

Indexed as

Cell NucleusEnzyme InhibitorsFarnesyltranstransferaseMutationNeoplasm ProteinsNeoplasmsNuclear EnvelopeNuclear ProteinsRepressor ProteinsCell Line, TumorHumansLamin Type BUbiquitinationEnzyme InhibitorsFarnesyltranstransferaseLamin Type BNeoplasm ProteinsNuclear ProteinsRepressor ProteinsSPOP protein, humanCancerCell biologyDrug therapyMolecular biologyTherapeutics

Identifiers

PMID40662365
PMCPMC12259254

What OpenQuestion holds

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Registered trials

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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.