Evaluating the Effect of Mutant EGFR on GPIT Subunit Expression in Glioblastoma Multiforme
Date of Award
Dr. Blake Johnson
Dr. Nathan Reyna
Dr. Randall Wight
The glycophosphatidylinositol (GPI) anchor is a lipid and glycan modification added to the C-terminus of substrate proteins in the endoplasmic reticulum via the multi-subunit GPI transamidase, or GPIT. Several subunits of GPIT, namely GPAA1, have previously been characterized as oncogenes across a variety of tumor types, specifically breast cancer where it contributes to enhanced cellular invasion. Using a C. septicum alpha toxin enrichment strategy, we have previously documented significantly elevated plasma levels of GPI anchored proteins occurring in glioma patients relative to non-malignant controls. Furthermore, we have previously uncovered significant increases in GPIT subunit levels, notably GPAA1, occurring in GBM relative to normal human astrocyte controls, which corresponded with increases in GPI anchored protein content. Interestingly, GPAA1 overexpression has previously been linked to physical association with EGFR in multiple epithelial tumor types, leading to increased GPIT activation via PIG-T and PIG-U phosphorylation . In this study, we aimed to evaluate the expression profile of the GPI biosynthesis pathway in the context of amplified, overexpressed, and/or mutant EGFR-GBM. Collectively, these studies will better our understanding of the oncogenic relationship between GPIT and EGFR and the therapeutic potential for GPIT inhibition in EGFR-positive GBM.
McCown, Sheldon, "Evaluating the Effect of Mutant EGFR on GPIT Subunit Expression in Glioblastoma Multiforme" (2020). Honors Theses. 771.