Subbalakshmi, AR and Sahoo, S and Biswas, K and Jolly, MK (2021) A Computational Systems Biology Approach Identifies SLUG as a Mediator of Partial Epithelial-Mesenchymal Transition (EMT). In: Cells Tissues Organs .
Full text not available from this repository.Abstract
Epithelial-mesenchymal plasticity comprises reversible transitions among epithelial, hybrid epithelial/mesenchymal (E/M) and mesenchymal phenotypes, and underlies various aspects of aggressive tumor progression such as metastasis, therapy resistance, and immune evasion. The process of cells attaining one or more hybrid E/M phenotypes is termed as partial epithelial mesenchymal transition (EMT). Cells in hybrid E/M phenotype(s) can be more aggressive than those in either fully epithelial or mesenchymal state. Thus, identifying regulators of hybrid E/M phenotypes is essential to decipher the rheostats of phenotypic plasticity and consequent accelerators of metastasis. Here, using a computational systems biology approach, we demonstrate that SLUG (SNAIL2)- A n EMT-inducing transcription factor-can inhibit cells from undergoing a complete EMT and thus stabilize them in hybrid E/M phenotype(s). It expands the parametric range enabling the existence of a hybrid E/M phenotype, thereby behaving as a phenotypic stability factor. Our simulations suggest that this specific property of SLUG emerges from the topology of the regulatory network it forms with other key regulators of epithelial-mesenchymal plasticity. Clinical data suggest that SLUG associates with worse patient prognosis across multiple carcinomas. Together, our results indicate that SLUG can stabilize hybrid E/M phenotype(s). © 2021
| Item Type: | Journal Article |
|---|---|
| Publication: | Cells Tissues Organs |
| Publisher: | S. Karger AG |
| Additional Information: | The copyright of this article belongs to S. Karger AG |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 09 Mar 2021 07:35 |
| Last Modified: | 09 Mar 2021 07:35 |
| URI: | http://eprints.iisc.ac.in/id/eprint/68116 |
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