Rue Ressler | 2024 I.S. Symposium

Name: Rue Ressler
Title: Cell on the Run! Boolean Modeling of the Migrating Epithelial Cell and Induction of Mesenchymal-Epithelial Transition by OVOL2 and GRHL2
Major: Biochemistry & Molecular Biology
Advisors: Erzsebet Regan; Stephanie Strand (second reader)

Metastasis remains the main reason for therapy failure and contributes to 90% of cancer patient deaths. During this process, tumor cells respond to mechanical cues from the changing microenvironment and demonstrate phenotypic plasticity to survive the volatile journey to a distant, secondary tumor site. Epithelial-mesenchymal plasticity (EMP) has been used to explain how a tumor cell gains metastatic potential as well as tumor-initiating ability, also known as cancer cell stemness. However, the correlation between EMP, cancer cell stemness and the role of the tumor microenvironment remains elusive. In order to characterize the role of mechanosensitivity in EMP and cancer cell stemness, we included two phenotypic stability factors (OVOL2 and GRHL2) which have been linked to cell migration and stemness into our 155 node Boolean model. The construction of this model led to the finding that OVOL2 and GRHL2 stabilize a novel migrating epithelial phenotype in low to moderately dense cellular environments on stiff extracellular matrix. Our observations contrast previous reports on OVOL2 and GRHL2 expression stabilizing the hybrid epithelial-mesenchymal state, as we found these transcription factors to be dispensable in the maintenance of this phenotype. These findings are critical as they broaden the view on how a tumor cell demonstrates phenotypic plasticity in different microenvironments and can tune epithelial-mesenchymal markers to stabilize different states along the spectrum of EMP.

Posted in Symposium 2024 on April 24, 2024.