Evidence map›Paper›PMID 42373888›Full record

ArticleEMBO molecular medicine2026

Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.

Julien P Gigan, Paulina Garcia-Gonzalez, Angelo Pilotti, Lou Galliot, Alexandre Reynaud, Yoan Ghaffar, Felipe Flores-Santibáñez, Sara Ghafoori, Eve Seillier, Rosario Lavignolle-Heguy and 12 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 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

22 authors.

Julien P GiganAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0000-0002-3799-6310
Paulina Garcia-GonzalezAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Angelo PilottiAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0009-0005-4288-1410
Lou GalliotAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Alexandre ReynaudAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Yoan GhaffarAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0009-0008-2937-4336
Felipe Flores-SantibáñezAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Sara GhafooriAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0009-0003-2335-6368
Eve SeillierAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Rosario Lavignolle-HeguyAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0000-0002-6642-3597
Daniela BarrosAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Caroline BretInstitute for Research in Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
Sharon FichauxAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Alexis CombesDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Alessandro BaniAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Rejane RuaAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.
Evelina GattiAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0000-0002-0667-0799
Béatrice Nal-RogierAix Marseille Université, CNRS, INSERM, CIML, Marseille, France.ORCID http://orcid.org/0000-0003-3452-7524
Stéphane RocchiUniversité Côte d'Azur, INSERM U1065, C3M, Nice, France.
Jérôme MoreauxCNRS UMR 9002-CNRS-UM - Institute of Human Genetics, Montpellier, France.ORCID http://orcid.org/0000-0002-5717-3207
Philippe Pierre *Aix Marseille Université, CNRS, INSERM, CIML, Marseille, France. pierre@ciml.univ-mrs.fr.ORCID http://orcid.org/0000-0003-0863-8255
Rafael J Argüello *Aix Marseille Université, CNRS, INSERM, CIML, Marseille, France. rafael.arguello@cnrs.fr.ORCID http://orcid.org/0000-0001-9785-3883

Funding

Agence Nationale de la Recherche (ANR) ANR-20-CE14-0028Agence Nationale de la Recherche (ANR) ANR-22-CE15-0015-02EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA) Immerge - 10111992EC | Horizon Europe | Global Challenges & European Industrial Competitiveness | HORIZON EUROPE Health (Santé) BeatsepInstitut National Du Cancer (INCa) HRHG Imagine projectInstitut National Du Cancer (INCa) SIRIC Pediacriex "SOUTH-Rock"Transcan (Transcan-3) https://transcan.eu/output-results/funded-projects/talete.kl
6 · The paper itself

Abstract

The unfolded protein response (UPR) is a stress-adaptation pathway and therapeutic target in cancer, yet its pro-survival versus pro-death outcome is difficult to predict because the three ER sensors, PERK, IRE1α, and ATF6, are highly interconnected. Transcriptomic analyses identified sensor-specific gene signatures associated with patient survival across malignancies, and indicated that low IRE1α activity (low XBP1 signature or higher expression of RIDD targets) correlates with improved outcome. We developed SNUPR (single nuclei analysis of the unfolded protein response), an accessible flow cytometry approach that profiles all three branches in nuclear suspensions. SNUPR reveals marked heterogeneity of UPR activation across cancer cell lines that cannot be inferred from sensor expression. This heterogeneity is derived from differences in the strength and duration of PERK-mediated translational inhibition, which gates downstream translation-dependent IRE1α and ATF6 transcriptional programs. Finally, in multiple myeloma, we show that bortezomib-tolerant cells depend on IRE1α activity for survival, linking UPR state to proteasome-inhibitor resistance and positioning SNUPR to guide branch-selective targeting.

Indexed as

Antineoplastic AgentsBoronic AcidsCell NucleusDrug Resistance, NeoplasmFlow CytometryMultiple MyelomaPyrazinesUnfolded Protein ResponseActivating Transcription Factor 6BortezomibCell Line, TumoreIF-2 KinaseEndoribonucleasesGene Expression ProfilingHumansProtein Serine-Threonine KinasesActivating Transcription Factor 6Antineoplastic AgentsATF6 protein, humanBoronic AcidsBortezomibeIF-2 KinaseEndoribonucleasesERN1 protein, humanProtein Serine-Threonine KinasesPyrazines

Identifiers

PMID42373888
PMCPMC13470223

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.