Evidence map›Paper›PMID 41821050›Full record

ArticleMolecular cancer2026

Context-dependent effect of glucocorticoid receptor activity shapes ovarian cancer cell plasticity and therapy response.

Micaela De Girolamo, Eduardo Ibello, Teresa Improda, Ilaria Tedesco, Carmela Dell'Aversana, Silvia Buonaiuto, Salvatore Arbucci, Cristina D'Aniello, Dario De Cesare, Renato Franco and 6 more

Abstract read
In one paragraph

Article in Molecular cancer, 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

16 authors.

Micaela De Girolamo *Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. de Crecchio 7, Naples, Italy.
Eduardo Ibello *Institute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Teresa ImprodaDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. de Crecchio 7, Naples, Italy.
Ilaria TedescoPathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni 5, Naples, Italy.
Carmela Dell'AversanaDepartment of Medicine and Surgery, LUM University, Casamassima, BA, Italy.
Silvia BuonaiutoInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Salvatore ArbucciInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Cristina D'AnielloInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Dario De CesareInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Renato FrancoPathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni 5, Naples, Italy.
Concetta AmbrosinoDepartment of Biology, University of Naples Federico II, Via Cinthia 26, Naples, Italy.
Lucia AltucciDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. de Crecchio 7, Naples, Italy.
Luigi CobellisDepartment of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. de Crecchio 2, Naples, Italy.
Eduardo J PatriarcaInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy.
Gabriella MinchiottiInstitute of Genetics and Biophysics (IGB) "A. Buzzati Traverso", Consiglio Nazionale delle Ricerche, CNR, Via P. Castellino, 111, Naples, Italy. gabriella.minchiotti@igb.cnr.it.
Gilda CobellisDepartment of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. de Crecchio 7, Naples, Italy. gilda.cobellis2@unicampania.it.

Funding

Fondazione AIRC per la ricerca sul cancro ETS IG32276Ministero dell'Università e della Ricerca (MUR-PRIN PNRR P20224ZY5P)Ministero dell'Università e della Ricerca PRIN PNRR P20224ZY5PNextGenerationEU Project D3 4 Health (PNC 0000001)
6 · The paper itself

Abstract

backgroundThe glucocorticoid receptor (GR) has been implicated in tumor progression and therapy resistance, yet its role in ovarian cancer (OC) remains controversial. In particular, how GR integrates environmental cues to control OC plasticity and therapeutic responses is poorly understood.

methodsWe investigated GR function in ovarian cancer (OC) cells by integrating genetic and pharmacological approaches. By using both OC cell lines and patient-derived cells, we performed a comprehensive set of phenotypic, molecular and functional assays alongside genome-wide transcriptomic analyses. We also extended these analyses to physiologically relevant 3D systems, including tumor spheroids and organotypic cultures, to better recapitulate the in vivo tumor microenvironment.

resultsWe provided unprecedented evidence that GR modulates OC behavior in a context-dependent manner. Under 2D culture conditions, GR enhanced cellular heterogeneity, epithelial–mesenchymal transition and migration, thereby increasing cisplatin resistance. Conversely, in a 3D context, GR exerted a marked yet reversible antiproliferative effect, characterized by reduced protein synthesis and adaptative stress responses. Mechanistically, GR activity converged on inhibition of glycolysis and activation of gluconeogenesis. Indeed, pharmacological inhibition of glycolysis with 2-deoxyglucose phenocopied GR-induced mesenchymalization in 2D cultures and growth inhibition in 3D models. Moreover, inhibition of gluconeogenesis with metformin prevented the GR-dependent antiproliferative effect in 3D models. Consistently, the glucocorticoid budesonide further potentiates the anti-proliferative effects of GR in OC spheroids. Transcriptomic analyses revealed that GR regulates gene programs involved in extracellular matrix organization and cell adhesion, uncovering a previously unrecognized role for GR in tumor microenvironment remodeling.

conclusionsOur findings reveal distinct, context-dependent effect of GR in OC cells, whereby GR activation promotes chemoresistance and migratory behavior in 2D cultures, while inducing a reversible slow proliferative state under 3D conditions. These results underscore the importance of cellular context in interpreting GR activity and suggest that selective GR modulators, including budesonide, may offer new therapeutic avenues for treating advanced-stage OC.

Indexed as

Cell PlasticityOvarian NeoplasmsReceptors, GlucocorticoidCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansTumor MicroenvironmentReceptors, Glucocorticoid3D ovarian cancer modelsCell-cell interactionsCell proliferationDrug resistanceGlucocorticoid receptor (GR)Metabolic reprogrammingOvarian cancer

Identifiers

PMID41821050
PMCPMC13195835

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.