Title: Uncovering the balance of phenotypic robustness and plasticity in metastasis-driving gene regulatory networks

Abstract: Metastasis, a hallmark of cancer, requires cells to both adapt to and withstand diverse biochemical and mechanical stresses as they migrate and colonize new tissues. While genetic mutations are the primary suspects behind cancer progression, they alone cannot fully explain metastatic capabilities. Key to metastatic success are two seemingly opposed traits: “phenotypic plasticity”, enabling cells to shift behaviors (e.g. immune evasion, adhesion changes), and “phenotypic robustness”, allowing cells to preserve advantageous traits despite environmental fluctuations.  Our research focuses on gene regulatory networks (GRNs) supporting Epithelial-Mesenchymal Plasticity (EMP), a pivotal process in metastasis. We show that GRN topologies reveal important insights into the coexistence of plasticity and robustness; notably, shared topological features like positive feedback loops underlie both traits, suggesting evolutionary selection for these patterns in metastatic cells. Targeting these network structures may offer new therapeutic strategies, reducing metastatic plasticity and robustness and thus impeding cancer cell adaptation and colonization.  Our findings provide potential paths for developing more targeted cancer therapies aimed at disrupting the adaptive potential of metastatic cells.

About the speaker: https://ctbp.northeastern.edu/2024/04/10/hari-kishore/

Video of the talk: https://youtu.be/3jhM4GVkKp8