[SS24] Recent Trends in Modeling & Simulation of Cancer

[SS24-03] Network topology and logic drives cell fate transitions in carcinomas

*MUBASHER RASHID RATHER¹ (1. INDIAN INSTITUTE OF TECHNOLOGY KANPUR (India))

Keywords:

cell fate transitions,Gene regulatory network,metastasis,phenotypic plasticity,mathematical modeling

Cells undergo fate transitions orchestrated by complex transcription factor networks, which are crucial for development, differentiation, and diseases like carcinoma metastasis. Understanding these transitions is vital for elucidating developmental processes and tumor heterogeneity driven by phenotypic plasticity. Using gene regulatory networks (GRNs) involved in epithelial-mesenchymal transition—a program enabling reversible transitions among epithelial, mesenchymal, and hybrid states—we investigate the interplay between network topology and cellular phenotypes. Our findings reveal that GRN topologies, including feedback loops, interaction consistency, and cohesion, provide insights into emergent dynamics and phenotypes. Mathematical models of two-component networks show that cooperativity and logic underlie robust phenotypic switches, enabling hysteretic or smooth state transitions. These transitions mimic processes like differentiation, trans-differentiation, and reprogramming, reflecting a dynamic epigenetic landscape. We also examined the role of intrinsic and extrinsic signals in modulating transitions, uncovering how network logic and signal asymmetry influence cellular reprogramming and differentiation. Different logics can drive cells toward distinct fates. Overall, our results highlight how GRN features and logic contribute to understanding fate transitions in development and carcinomas. These insights could inform targeted cancer therapies to disrupt metastatic adaptability and strategies for engineering cell fates in synthetic biology and regenerative medicine.