Metabolic Dysregulation: An Investigation of the Role of FOXO3 in Gluconeogensis in PTEN-Null Glioblastomas

Author

Victor Fanniel, The University of Texas Rio Grande Valley

Date of Award

5-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Megan Keniry

Second Advisor

Dr. Robert Gilkerson

Third Advisor

Dr. Michael Persans

Abstract

Many processes are regulated by the Phosphatidylinositol 3 kinase (PI3K) pathway in the cell including cell survival, metabolism, and apoptosis. Increased activation of the PI3K pathway is a hallmark of many cancers which can be oftentimes attributed to the mutation of PTEN, which encodes an enzyme that performs the reverse reaction of PI3K. When PTEN is null-mutated, this creates a constitutively active PI3K pathway and constitutively active AKT. Since AKT phosphorylates conserved residues on FOXO transcription factors to mark them for nuclear export, this renders FOXO inactive. However, new research has provided evidence that FOXO is still present in the nucleus of at least some of these PTEN-null cancer cells, and that this FOXO is still promoting transcription despite high AKT output in certain highly aggressive cancer and embryonic stem cells. We show that in a PTEN-null glioblastoma setting, FOXO is still active and regulates PEPCK (regulator of gluconeogenesis) expression despite high output of PI3K.

Comments

Copyright 2018 Victor Eric Michael Fanniel. All Rights Reserved.

https://www.proquest.com/dissertations-theses/metabolic-dysregulation-investigation-role-foxo3/docview/2097244914/se-2?accountid=7119

Recommended Citation

Fanniel, Victor, "Metabolic Dysregulation: An Investigation of the Role of FOXO3 in Gluconeogensis in PTEN-Null Glioblastomas" (2018). Theses and Dissertations. 231.
https://scholarworks.utrgv.edu/etd/231