Evidence map›Paper›PMID 36460775›Full record

ArticleCell death and differentiation2023

Caspase-8 as a novel mediator linking Src kinase signaling to enhanced glioblastoma malignancy.

Claudia Contadini, Alessandra Ferri, Marta Di Martile, Claudia Cirotti, Donatella Del Bufalo, Francesca De Nicola, Matteo Pallocca, Maurizio Fanciulli, Francesca Sacco, Gloria Donninelli and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
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

12 citing papers in PubMed, 17 citations in OpenAlex.

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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

18 authors at 4 institutions in 2 countries.

Claudia ContadiniDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Alessandra FerriDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Marta Di MartileUOSD Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Claudia CirottiDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Donatella Del BufaloUOSD Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.ORCID 0000-0002-3148-6096
Francesca De NicolaUOSD SAFU, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Matteo PalloccaUOSD SAFU, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Maurizio FanciulliUOSD SAFU, IRCCS Regina Elena National Cancer Institute, Rome, Italy.ORCID 0000-0002-5281-4191
Francesca SaccoDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.
Gloria DonninelliLaboratory of Molecular Neuroimmunology, IRCCS-Fondazione Santa Lucia, 00179, Rome, Italy.
Alessia CaponeLaboratory of Molecular Neuroimmunology, IRCCS-Fondazione Santa Lucia, 00179, Rome, Italy.
Elisabetta VolpeLaboratory of Molecular Neuroimmunology, IRCCS-Fondazione Santa Lucia, 00179, Rome, Italy.ORCID 0000-0001-7985-2422
Nadine KellerUniversity of California San Diego Moores Cancer Center, La Jolla, CA, 92093-0803, USA.
Shunichiro MikiDepartment of Medicine, Division of Regenerative Medicine, University of California-San Diego, La Jolla, CA, 92093, USA.
Daisuke KawauchiDepartment of Medicine, Division of Regenerative Medicine, University of California-San Diego, La Jolla, CA, 92093, USA.
Dwayne StupackUniversity of California San Diego Moores Cancer Center, La Jolla, CA, 92093-0803, USA.
Frank FurnariDepartment of Medicine, Division of Regenerative Medicine, University of California-San Diego, La Jolla, CA, 92093, USA.
Daniela BarilàDepartment of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy. daniela.barila@uniroma2.it.ORCID 0000-0002-6192-1562
Istituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of California San Diego · USUniversity of Rome Tor Vergata · ITFondazione Santa Lucia · IT

Funding

Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5M
Credentialing next-generation human glioma models for precision therapeuticsR01CA258248 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Frank Furnari, Christopher Ryan Miller · 2022 to 2026
$3.0M
Biophysical Interrogation of Signals that Drive GBM InvasionR01NS116802 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ENGLER, ADAM J, FURNARI, FRANK · 2020 to 2024
$2.3M
Genotypic Interactions in Brain Cancer HeterogeneityR56NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2023 to 2023
$537k
NCI NIH HHS R01 CA258248NINDS NIH HHS R01 NS080939NINDS NIH HHS R01 NS116802NINDS NIH HHS R56 NS080939
6 · The paper itself

Abstract

Caspase-8 is a cysteine protease that plays an essential role in apoptosis. Consistently with its canonical proapoptotic function, cancer cells may genetically or epigenetically downregulate its expression. Unexpectedly, Caspase-8 is often retained in cancer, suggesting the presence of alternative mechanisms that may be exploited by cancer cells to their own benefit. In this regard, we reported that Src tyrosine kinase, which is aberrantly activated in many tumors, promotes Caspase-8 phosphorylation on Tyrosine 380 (Y380) preventing its full activation. Here, we investigated the significance of Caspase-8 expression and of its phosphorylation on Y380 in glioblastoma, a brain tumor where both Caspase-8 expression and Src activity are often aberrantly upregulated. Transcriptomic analyses identified inflammatory response as a major target of Caspase-8, and in particular, NFκB signaling as one of the most affected pathways. More importantly, we could show that Src-dependent phosphorylation of Caspase-8 on Y380 drives the assembly of a multiprotein complex that triggers NFκB activation, thereby inducing the expression of inflammatory and pro-angiogenic factors. Remarkably, phosphorylation on Y380 sustains neoangiogenesis and resistance to radiotherapy. In summary, our work identifies a novel interplay between Src kinase and Caspase-8 that allows cancer cells to hijack Caspase-8 to sustain tumor growth.

Indexed as

Caspase 8Glioblastomasrc-Family KinasesApoptosisCaspase 3HumansPhosphorylationSignal TransductionCaspase 3Caspase 8src-Family Kinases

Identifiers

PMID36460775
PMCPMC9950463
OpenAlexW4310641546

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.