Evidence map›Paper›PMID 42230533›Full record

ArticleCell death & disease2026

USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.

Danielle Meiwen Fang, Raj K Shrestha, Beatriz German, Razia Rahman, Scott L Townley, Jianling Xie, Adrienne R Hanson, Richard Iggo, Zeyad D Nassar, Madison Helm and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Danielle Meiwen FangFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Raj K ShresthaFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Beatriz GermanCenter for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID http://orcid.org/0009-0004-5105-4583
Razia RahmanFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.ORCID http://orcid.org/0009-0001-5124-1352
Scott L TownleyFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Jianling XieFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-0588-8016
Adrienne R HansonFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Richard IggoDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Zeyad D NassarSouth Australian Health and Medical Research Institute, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-7779-2697
Madison HelmSouth Australian Health and Medical Research Institute, Adelaide, SA, Australia.
Shashikanth MarriFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Alex D ColellaFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Giles BestFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Margaret M CenteneraSouth Australian Health and Medical Research Institute, Adelaide, SA, Australia.
Wayne D TilleyDame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Tim K ChatawayFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Leigh EllisCenter for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Lisa M ButlerSouth Australian Health and Medical Research Institute, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0003-2698-3220
Luke A SelthFlinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. luke.selth@flinders.edu.au.ORCID http://orcid.org/0000-0002-4686-1418

Funding

Cancer Australia 2020_PdCCRS_2001432Cancer Australia 2023_PCRS_0269Cancer Council NSW (Cancer Council New South Wales) RG 23-04Cancer Council NSW (Cancer Council New South Wales) RG 25-13Cancer Council South Australia PRF2919Hospital Research Foundation (The Hospital Research Foundation) 2022-CP-IDMH-019
6 · The paper itself

Abstract

In prostate cancer, the development of resistance to androgen receptor (AR)-targeted therapies (ATTs) and chemotherapies is associated with the emergence of new phenotypic states with altered molecular features. Here, we identify ubiquitin-specific peptidase 2 (USP2) as a mediator of this phenomenon. USP2 is induced in response to ATTs and more highly expressed in aggressive, castration-resistant prostate tumours that have lost dependence on AR as an oncogenic driver. Overexpression of USP2 in prostate cancer cells elicited elevated rates of glycolysis, neuroendocrine features and resistance to docetaxel, an important chemotherapeutic agent for advanced prostate cancer. USP2 stabilised key oncoproteins, including Aurora kinase A, cyclin D1 and fatty acid synthase. An unbiased proteomic approach identified potential new USP2 substrates and a USP2-regulated proteome that is associated with metastatic disease. Genetic or pharmacological targeting of USP2 caused cell death in human and mouse models of aggressive prostate cancer and the USP2 inhibitor ML364 exhibited potent anti-tumour effects against an orthotopic xenograft model of AR-null disease. Collectively, this study identifies USP2 as a critical regulator of proteins involved in prostate cancer progression and therapy resistance, positioning it as a viable therapeutic target.

Indexed as

AndrogensDrug Resistance, NeoplasmEndopeptidasesOncogene ProteinsProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantUbiquitin ThiolesteraseAnimalsCell Line, TumorDocetaxelHumansMaleMiceReceptors, AndrogenXenograft Model Antitumor AssaysAndrogensDocetaxelEndopeptidasesOncogene ProteinsReceptors, AndrogenUbiquitin ThiolesteraseUSP2 protein, human

Identifiers

PMID42230533
PMCPMC13443806

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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.