Theses and Dissertations

Date of Award

5-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Megan Keniry

Second Advisor

Robert Gilkerson

Third Advisor

Matthew Terry

Abstract

Glioblastoma Multiforme (GBM) is an aggressive cancer with patients surviving 13 months on average after diagnosis. The PI3K-PKB/AKT pathway is conserved from flies to mammals. The PI3K signaling pathway aids in the growth and survival of tumor cells. Forkhead box transcription factors subclass O (FOXO1, FOXO3, and FOXO4) act as tumor suppressors in some contexts. In GBM, our group and others showed that FOXO transcription factors drive stem gene expression to promote growth and survival. We disrupted the FOXO4 gene in U87MG cells using CRISPR Cas9 genome editing and performed RNA-seq to identify targets of this transcription factor. FOXO4 loss led to significantly reduced LIF and SESN3 gene expression. Both LIF and SESN3 promote PI3K Pathway output. Based on this, we examined PI3K output by assessing ser/thr kinase AKT activation and discovered a two-fold reduction in the FOXO4 mutants. More tests must be done to investigate the role of FOXO4 target genes LIF and SESN3 on AKT activity in the setting of GBM including impacts on chemotherapeutic efficacy.

Comments

Copyright 2024 David Uribe.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/pqdtglobal1/dissertations-theses/foxo4-impacts-akt-glioblastoma-multiforme/docview/3085313053/sem-2?accountid=7119

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