Evidence map›Paper›PMID 41053176›Full record

ArticleCell death and differentiation2025

Caspase-8 expression and its Src dependent phosphorylation on Tyrosine 380 triggers NRF2 signaling activation in glioblastoma.

Claudia Cirotti, Claudia Di Girolamo, Irene Taddei, Claudia Contadini, Giorgia Massacci, Francesca Sacco, Donatella Del Bufalo, Illari Salvatori, Cristiana Valle, Daniela Barilà

Abstract read
In one paragraph

Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. PANoptosis and Immune Remodeling in the Tumor Microenvironment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  4. Review
  5. Review
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

10 authors.

Claudia CirottiDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy. claudia.cirotti@uniroma2.it.ORCID 0000-0001-6267-8034
Claudia Di GirolamoLaboratory of Cell Signaling, IRCCS-Fondazione Santa Lucia, 00179, Rome, Italy.
Irene TaddeiLaboratory of Cell Signaling, IRCCS-Fondazione Santa Lucia, 00179, Rome, Italy.
Claudia ContadiniDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Giorgia MassacciDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.ORCID 0000-0003-3223-6547
Francesca SaccoDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.ORCID 0000-0001-5586-9529
Donatella Del BufaloPreclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, 00144, Rome, Italy.ORCID 0000-0002-3148-6096
Illari SalvatoriInstitute of Translational Pharmacology (IFT), Consiglio Nazionale Delle Ricerche (CNR), Rome, Italy.
Cristiana ValleInstitute of Translational Pharmacology (IFT), Consiglio Nazionale Delle Ricerche (CNR), Rome, Italy.
Daniela BarilàDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy. daniela.barila@uniroma2.it.ORCID 0000-0002-6192-1562

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) AIRC-IG2021-n.26230Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) PRIN-2022 20222KSN2N
6 · The paper itself

Abstract

Caspase-8 expression is upregulated in many tumors where, despite its canonical apoptotic pathway, it sustains cancer progression promoting cell migration, NF-kB activation and inflammation. Here, we provide the first evidence for a novel role of Caspase-8 in promoting the metabolic rewiring of cancer cells. By performing transcriptomic, proteomic and phosphoproteomic analyses on glioblastoma cellular models, we identify Caspase-8 as an unexpected modulator of NRF2. Here we show that Caspase-8 expression and phosphorylation affect NRF2 activity and mitochondrial homeostasis. Mechanistically, we demonstrate that Src-dependent phosphorylation of Caspase-8 on Tyrosine 380 (Y380), frequently reported in cancers including glioblastoma, sustains mTORC1 activation, thus promoting energy metabolism. mTORC1 activity results in p62 phosphorylation allowing its dependent sequestration of KEAP1 protein and constitutive NRF2 signaling activation, as a consequence. Overall, this work depicted a novel unexpected role for Caspase-8 in the modulation of cancer cell metabolism, bridging together Src, mTORC1 and NRF2 signaling.

Indexed as

Caspase 8GlioblastomaNF-E2-Related Factor 2src-Family KinasesCell Line, TumorHumansKelch-Like ECH-Associated Protein 1Mechanistic Target of Rapamycin Complex 1MitochondriaPhosphorylationSignal TransductionTyrosineCASP8 protein, humanCaspase 8Kelch-Like ECH-Associated Protein 1Mechanistic Target of Rapamycin Complex 1NFE2L2 protein, humanNF-E2-Related Factor 2src-Family KinasesTyrosine

Identifiers

PMID41053176
PMCPMC12669649

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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.