Increased Expression of SREBP-1 and its Downstream Targets in Medulloblastoma Open Access

Abstract

Medulloblastoma (MB) is one the most common malignant brain tumors diagnosed in children. While clinical presentation and health outcomes vary depending on the MB subgroup classification, current standard lines of treatment are highly toxic and invasive, and recurrences are often fatal. Due to the bioenergetic and biosynthetic requirements of tumor cells, many cancers demonstrate metabolic reprogramming to maintain and promote tumorigenesis. Specifically, lipid metabolism pathways have been reported to be enhanced in many cancer types, such as gliomas. Within lipid metabolism sterol regulatory element-binding proteins (SREBPs) are crucial regulators of fatty acid synthesis, cholesterol homeostasis, and glucose metabolism. In this study, we examine the expression of SREBP-1 and its downstream targets—fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), and ATP citrate lyase (ACLY) —in MB. Using Western blot, real-time qPCR, and immunofluorescence staining, our findings indicate that SREBP-1 and its downstream targets are upregulated in MB with similar expression levels across various MB subgroup cell lines. Therefore, our study demonstrates that SREBP-1 may be a potential therapeutic target in treating MB. 

Table of Contents

Introduction ...................................................................................................................................1 

Hypothesis and Aims ....................................................................................................................7 

Materials and Methods .................................................................................................................8 

Results ..........................................................................................................................................12 

Discussion ....................................................................................................................................21 

References ....................................................................................................................................25 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Biology, Cell Health Sciences, Oncology
Keyword	Cancer Metabolism SREBP1 Medulloblastoma Neuro-Oncology
Committee Chair / Thesis Advisor	Kenney, Anna, Emory University
Committee Members	Shanmugam, Mala, Emory University Eisen, Arri, Emory University

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