Evidence map›Paper›PMID 36431901›Full record

ArticleMolecules (Basel, Switzerland)2022

Identification of Dihydrolipoamide Dehydrogenase as Potential Target of Vemurafenib-Resistant Melanoma Cells.

Claudio Tabolacci, Deborah Giordano, Stefania Rossi, Martina Cordella, Daniela D'Arcangelo, Federica Moschella, Stefania D'Atri, Mauro Biffoni, Angelo Facchiano, Francesco Facchiano

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. 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
0.8field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.Apoptosis : an international journal on programmed cell death · 2024
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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

10 authors at 3 institutions in 1 country.

Claudio TabolacciDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0001-5001-285X
Deborah GiordanoNational Research Council, Institute of Food Science, Via Roma 64, 83110 Avellino, Italy.ORCID 0000-0002-5838-1913
Stefania RossiDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0002-8854-7072
Martina CordellaDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Daniela D'ArcangeloLaboratory of Molecular Oncology, IDI-IRCCS, 00167 Rome, Italy.
Federica MoschellaDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0002-1965-6523
Stefania D'AtriLaboratory of Molecular Oncology, IDI-IRCCS, 00167 Rome, Italy.
Mauro BiffoniDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Angelo FacchianoNational Research Council, Institute of Food Science, Via Roma 64, 83110 Avellino, Italy.ORCID 0000-0002-7077-4912
Francesco FacchianoDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0003-4313-0617
Istituto Superiore di Sanità · ITInstitute of Food Science · ITIstituto Dermopatico dell'Immacolata · IT

Funding

Banca d'Italia Contributo LiberaleItalian Ministry of Health Italy-USA Oncoproteomic ProgramItalian Ministry of Health RC 2021, line-3.4
6 · The paper itself

Abstract

backgroundDespite recent improvements in therapy, the five-year survival rate for patients with advanced melanoma is poor, mainly due to the development of drug resistance. The aim of the present study was to investigate the mechanisms underlying this phenomenon, applying proteomics and structural approaches to models of melanoma cells.

methodsSublines from two human (A375 and SK-MEL-28) cells with acquired vemurafenib resistance were established, and their proteomic profiles when exposed to denaturation were identified through LC-MS/MS analysis. The pathways derived from bioinformatics analyses were validated by in silico and functional studies.

resultsThe proteomic profiles of resistant melanoma cells were compared to parental counterparts by taking into account protein folding/unfolding behaviors. Several proteins were found to be involved, with dihydrolipoamide dehydrogenase (DLD) being the only one similarly affected by denaturation in all resistant cell sublines compared to parental ones. DLD expression was observed to be increased in resistant cells by Western blot analysis. Protein modeling analyses of DLD's catalytic site coupled to in vitro assays with CPI-613, a specific DLD inhibitor, highlighted the role of DLD enzymatic functions in the molecular mechanisms of BRAFi resistance.

conclusionsOur proteomic and structural investigations on resistant sublines indicate that DLD may represent a novel and potent target for overcoming vemurafenib resistance in melanoma cells.

Indexed as

Dihydrolipoamide DehydrogenaseMelanomaCell Line, TumorChromatography, LiquidDrug Resistance, NeoplasmHumansProteomicsProto-Oncogene Proteins B-rafTandem Mass SpectrometryVemurafenibDihydrolipoamide DehydrogenaseProto-Oncogene Proteins B-rafVemurafenibBRAFi resistanceCPI-613dihydrolipoamide dehydrogenasemelanomaprotein structureproteomicstargeted therapy

Identifiers

PMID36431901
PMCPMC9698468
OpenAlexW4309003323

What OpenQuestion holds

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LicenceCC BY
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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.