Evidence map›Paper›PMID 38787503›Full record

ArticleMolecular biology reports2024

ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2).

Nirajan Ghosal, Poulami Tapadar, Divisha Biswas, Ranjana Pal

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Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Nirajan GhosalDepartment of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India.
Poulami TapadarDepartment of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India.
Divisha BiswasDepartment of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India.
Ranjana PalDepartment of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India. ranjana.dbs@presiuniv.ac.in.ORCID http://orcid.org/0000-0002-9824-6337

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTRAIL protein on binding to its cognate death receptors (DR) can induce apoptosis specifically in breast tumor cells sparing normal cells. However, TRAIL also binds to decoy receptors (DCR) thereby inhibiting the apoptotic pathways thus causing TRAIL resistance. Also, one of the barriers due to which TRAIL-based therapy could not become FDA-approved might be because of resistance to therapy. Therefore, in the current study we wanted to explore the role of transcription factors in TRAIL resistance with respect to breast cancer.

methodsMicroarray data from TRAIL-sensitive (TS) and TRAIL-resistant (TR) MDA-MB-231 cells were reanalyzed followed by validation of the candidate genes using quantitative PCR (qPCR), immunoblotting and immunofluorescence technique. Overexpression of the candidate gene was performed in MDA-MB-231 and MCF7 cells followed by cell viability assay and immunoblotting for cleaved caspase-3. Additionally, immunoblotting for DCR2 was carried out. TCGA breast cancer patient survival was used for Kaplan-Meier (KM) plot.

resultsValidation of the candidate gene i.e. ELF3 using qPCR and immunoblotting revealed it to be downregulated in TR cells compared to TS cells. ELF3 overexpression in MDA-MB-231 and MCF7 cells caused reversal of TRAIL resistance as observed using cell viability assay and cleaved caspase-3 immunoblotting. ELF3 overexpression also resulted in DCR2 downregulation in the MDA-MB-231 and MCF7 cells. Furthermore, KM analysis found high ELF3 and low DCR2 expression to show better patient survival in the presence of TRAIL.

conclusionOur study shows ELF3 to be an important factor that can influence TRAIL-mediated apoptosis in breast cancer. Also, ELF3 and DCR2 expression status should be taken into consideration while designing strategies for successful TRAIL-based therapy.

Indexed as

ApoptosisBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticTNF-Related Apoptosis-Inducing LigandTranscription FactorsCell Line, TumorCell SurvivalFemaleHumansMCF-7 CellsProto-Oncogene Proteins c-etsReceptors, Tumor Necrosis Factor, Member 10cTumor Necrosis Factor Decoy ReceptorsDNA-Binding ProteinsELF3 protein, humanProto-Oncogene Proteins c-etsReceptors, Tumor Necrosis Factor, Member 10cTNF-Related Apoptosis-Inducing LigandTNFRSF10D protein, humanTNFSF10 protein, humanTranscription FactorsTumor Necrosis Factor Decoy ReceptorsApoptosisBreast cancerELF3 transcription factorMicroarrayTRAIL resistance

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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.