Subbalakshmi, AR and Sahoo, S and Manjunatha, P and Goyal, S and Kasiviswanathan, VA and Mahesh, Y and Ramu, S and McMullen, I and Somarelli, JA and Jolly, MK (2023) The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition. In: Journal of Biological Engineering, 17 (1).
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Abstract
Background: Epithelial-mesenchymal plasticity (EMP) involves bidirectional transitions between epithelial, mesenchymal and multiple intermediary hybrid epithelial/mesenchymal phenotypes. While the process of epithelial-mesenchymal transition (EMT) and its associated transcription factors are well-characterised, the transcription factors that promote mesenchymal-epithelial transition (MET) and stabilise hybrid E/M phenotypes are less well understood. Results: Here, we analyse multiple publicly-available transcriptomic datasets at bulk and single-cell level and pinpoint ELF3 as a factor that is strongly associated with an epithelial phenotype and is inhibited during EMT. Using mechanism-based mathematical modelling, we also show that ELF3 inhibits the progression of EMT. This behaviour was also observed in the presence of an EMT inducing factor WT1. Our model predicts that the MET induction capacity of ELF3 is stronger than that of KLF4, but weaker than that of GRHL2. Finally, we show that ELF3 levels correlates with worse patient survival in a subset of solid tumour types. Conclusion: ELF3 is shown to be inhibited during EMT progression and is also found to inhibit the progression of complete EMT suggesting that ELF3 may be able to counteract EMT induction, including in the presence of EMT-inducing factors, such as WT1. The analysis of patient survival data indicates that the prognostic capacity of ELF3 is specific to cell-of-origin or lineage. © 2023, The Author(s).
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Biological Engineering |
| Publisher: | BioMed Central Ltd |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | kruppel like factor 4; protein E74 like factor 3; transcription factor; unclassified drug; WT1 protein, Article; cancer survival; cell level; cohort analysis; controlled study; epithelial mesenchymal transition; epithelium cell; gene; GRHL2 gene; human; human cell; mathematical model; prediction; prognosis; single cell analysis; transcriptomics |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 03 Apr 2023 09:25 |
| Last Modified: | 03 Apr 2023 09:25 |
| URI: | https://eprints.iisc.ac.in/id/eprint/81139 |
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