EXPLORING THE IMPACT OF HYPOXIA ON INDUCING EPITHELIAL-MESENCHYMAL TRANSITION IN EWING'S SARCOMA CELLS: A COMPUTATIONAL MODEL

Daner Acunha Silveira; Shantanu Gupta; André Tesainer Brunetto; José Carlos Merino Mombach; Marialva Sinigaglia

Paper Title

Authors

Daner Acunha Silveira
Shantanu Gupta
André Tesainer Brunetto
José Carlos Merino Mombach
Marialva Sinigaglia

Modality

Poster

Subject area

Systems Biology and Modeling

Publishing Date

21/11/2024

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting-2024/832072-exploring-the-impact-of-hypoxia-on-inducing-epithelial-mesenchymal-transition-in-ewings-sarcoma-cells--a-computa

ISBN

978-65-272-0843-3

Keywords

Hypoxia, epitelial-mesenchymal transition, ewing sarcoma, computational modeling, hybrid phenotype

Summary

Ewing's Sarcoma (ES) often exhibits hypoxic tumor regions, which may correlate with metastatic dissemination and, consequently, epithelial-mesenchymal transition (EMT). EMT is a biological process facilitating tumor migration, characterized by a phenotypic shift from epithelial to mesenchymal cells. Previous studies across various tumors have indicated the stabilization of a hybrid phenotype during EMT, which displays higher metastatic potential and/or drug resistance than purely epithelial or mesenchymal cells. Nevertheless, the existence and stabilization mechanism of this hybrid phenotype under hypoxia in ES remain elusive. In this study, we investigated the induction of this phenotype through a proposed computational model, using biochemical insights on ES cells from existing literature. We translated this data into a network of molecular interactions and modeled the dynamics of node activation and inactivation using logical operators such as AND, OR, and NOT. Model validation was achieved by aligning simulations of node perturbations (either gain or loss of function) with corresponding experimental data reported in the literature. The wild-type simulation of the model revealed 10 stable states, categorized into epithelial (4), hybrid (4), and mesenchymal (2) phenotypes. Consequently, we explored the positive circuits responsible for stabilizing observed hybrid states. Our model suggests that circuits involving molecules such as ZEB2, miR-145, miR-200, miR-129, and TWIST1 may contribute to hybrid state stabilization during EMT. Loss of function of any of these components resulted in the destabilization of the hybrid states in the model. These findings underscore the significance of these molecules in stabilizing hybrid phenotypes and highlight their potential as targets for therapeutic interventions in ES. Identification of unexplored regulatory mechanisms governing EMT in ES holds promise for the development of novel therapeutic strategies.

Title of the Event: 20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event: Salvador
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

SILVEIRA, Daner Acunha et al.. EXPLORING THE IMPACT OF HYPOXIA ON INDUCING EPITHELIAL-MESENCHYMAL TRANSITION IN EWING'S SARCOMA CELLS: A COMPUTATIONAL MODEL.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/832072-EXPLORING-THE-IMPACT-OF-HYPOXIA-ON-INDUCING-EPITHELIAL-MESENCHYMAL-TRANSITION-IN-EWINGS-SARCOMA-CELLS--A-COMPUTA. Access in: 16/07/2025