Evidence map›Paper›PMID 37398064›Full record

ArticlebioRxiv : the preprint server for biology2023

The landscape of cancer rewired GPCR signaling axes.

Chakit Arora, Marin Matic, Pierluigi DiChiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe Diaferia, Ranka Vukotic and 5 more

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 6 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Chakit AroraLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Marin MaticLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Pierluigi DiChiaroDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy.
Natalia De Oliveira RosaLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Francesco CarliLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Lauren ClubbDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Lorenzo Amir Nemati FardLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Giorgos KargasLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Giuseppe DiaferiaDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy.
Ranka VukoticAzienda Ospedaliero-Universitaria Pisana, Via Roma, 67, 56126 Pisa.
Luana LicataDepartment of Biology, University of Rome 'Tor Vergata', Rome 00133, Italy.
Guanming WuDivision of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, USA.
Gioacchino NatoliDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy.
J Silvio GutkindDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Francesco RaimondiLaboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy.
Scuola Normale Superiore · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of California San Diego · USAzienda Ospedaliera Universitaria Pisana · ITOregon Health & Science University · USUniversity of Rome Tor Vergata · IT

Funding

Reactome - CoreU41HG003751 · NHGRI · ONTARIO INSTITUTE FOR CANCER RESEARCH · PI STEIN, LINCOLN D. · 2012 to 2021
$14.5M
Reactome: An Open Knowledgebase of Human Pathways.U24HG012198 · NHGRI · ONTARIO INSTITUTE FOR CANCER RESEARCH · PI Marc E Gillespie, LINCOLN D. STEIN · 2022 to 2026
$7.0M
NHGRI NIH HHS U24 HG012198NHGRI NIH HHS U41 HG003751
6 · The paper itself

Abstract

We explored the dysregulation of GPCR ligand signaling systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes, which revealed that multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes. We showed that biosynthetic pathway enrichment from enzyme expression recapitulated pathway activity signatures from metabolomics datasets, providing valuable surrogate information for GPCRs responding to organic ligands. We found that several GPCRs signaling components were significantly associated with patient survival in a cancer type-specific fashion. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many pairs involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including e.g., muscarinic, adenosine, 5-hydroxytryptamine and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).

Identifiers

PMID37398064
PMCPMC10312480
OpenAlexW4324134344

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.