Evidence map›Paper›PMID 40083690›Full record

ArticleInternational journal of biological sciences2025

PSMC6 regulation of ovarian cancer cisplatin resistance unravels a new mode for proteasome targeting.

Matteo Costantino, Luca Mirra, Padraig D'arcy, Cristina Corno, Nives Carenini, Elisabetta Corna, Johannes Gubat, Chiara M Ciniselli, Pietro Pratesi, Paolo Verderio and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

13 authors.

Matteo CostantinoUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Luca MirraUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Padraig D'arcyDepartment of Biomedical and Clinical Sciences, Linköping University, Sweden.
Cristina CornoUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Nives CareniniUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Elisabetta CornaUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Johannes GubatDepartment of Biomedical and Clinical Sciences, Linköping University, Sweden.
Chiara M CiniselliUnit of Bioinformatics and Biostatistics, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133 Milan, Italy.
Pietro PratesiUnit of Bioinformatics and Biostatistics, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133 Milan, Italy.
Paolo VerderioUnit of Bioinformatics and Biostatistics, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133 Milan, Italy.
Stig LinderDepartment of Biomedical and Clinical Sciences, Linköping University, Sweden.
Giovanni L BerettaUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Paola PeregoUnit of Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ovarian carcinoma has still a poor prognosis. CRISPR/Cas9 loss-of-function screen revealed a relationship between the PSMC6 proteasome subunit expression and survival of cisplatin-sensitive and -resistant ovarian carcinoma cells. Increased levels of PSMC6 were evidenced in multiple ovarian carcinoma cell lines versus normal cells. An association between PSMC6 levels and tumour stages as well as with a reduced progression-free survival was found. Since a PSMC6 interactome analysis evidenced limited knowledge on PSMC6 biology, mechanistic studies were carried out. PSMC6 knockdown indicated reduced cell growth and clonogenicity in cisplatin-sensitive IGROV-1 and -resistant IGROV-1/Pt1 cells, with a higher impact in resistant cells. This behaviour was accompanied by the accumulation of ubiquitinated proteins and down-regulation of ERK1/2 phosphorylation mediated by increased DUSP6. PSMC6 silencing increased sensitivity to cisplatin in IGROV-1/Pt1 cells as shown by clonogenic assay and 3D spheroids. Since PSMC6 knockdown did not change sensitivity to 20S and 19S proteasome inhibitors, we suggest a new mode of proteasome targeting by interference with a proteasome ATPase. Overall, a link between PSMC6 and ovarian carcinoma aggressiveness is envisioned, highlighting PSMC6 as a potential diagnostic and therapeutic target.

Indexed as

Antineoplastic AgentsCisplatinDrug Resistance, NeoplasmOvarian NeoplasmsProteasome Endopeptidase ComplexCell Line, TumorCell ProliferationFemaleHumansAntineoplastic AgentsCisplatinProteasome Endopeptidase Complexcisplatindrug resistanceDUSP6ovarian carcinomaproteasomePSMC6

Identifiers

PMID40083690
PMCPMC11900818

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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.