Theses and Dissertations

Date of Award

7-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Megan Keniry

Second Advisor

Robert Gilkerson

Third Advisor

Christopher Vitek

Abstract

Glioblastoma Multiforme (GBM) is an aggressive astrocytoma tumor type with a poor prognosis and limited immunotherapeutic options for those inflicted. Stem gene expression of this cancer indicates a direct relationship with the transcription factors, Forkhead box subfamily O (FOXO-1, -3 and - 4). These transcription factors are evolutionarily conserved, partially redundant. They are involved in diverse and fundamental biological processes such as cell survival, stem cell homeostasis, cell fate determination, cell cycle maintenance, metabolism, and apoptosis. Increasing evidence suggests interconnectivity between the WNT Pathway and FOXO transcription factors; however, the mechanism and full extent to which these interactions play a role in determining FOXO output is yet to be delineated. Under oxidative stress seen in colon cancer, myoblasts, and osteoblasts, FOXO factors hinder canonical WNT pathway output by disrupting the interaction between beta-catenin and TCF4. Through a genomics and CRISPR Cas9 genome editing approach, the Keniry et al. laboratory is the first to report that FOXO factors promote canonical WNT Pathway gene expression in glioblastoma cells. ChIP-Seq analysis with FOXO1, FOXO3, and FOXO4 antibodies revealed TCF7 as an integral target. Therefore, it is hypothesized that FOXO factors promote WNT Pathway output through the induction of TCF7 to impact proliferation, colony formation, and cancer stem cell maintenance.

Comments

Copyright 2025 Stephanie Oyervides. All Rights Reserved. https://proquest.com/docview/3253954141

Download

Included in

Genetics Commons

Share

COinS