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

Autor: Ghosal N; Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India., Tapadar P; Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India., Biswas D; Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India., Pal R; Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India. ranjana.dbs@presiuniv.ac.in.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 May 24; Vol. 51 (1), pp. 671. Date of Electronic Publication: 2024 May 24.
DOI: 10.1007/s11033-024-09615-1
Abstrakt: Background: TRAIL 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.
Methods: Microarray 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.
Results: Validation 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.
Conclusion: Our 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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