Nuclear receptor TLX and dietary habits: Identifying new targets for the treatment and prevention of metastatic breast cancer

As the most diagnosed cancer worldwide, breast cancer is one of the most significant modern global public health challenges we currently face. While advances in early detection and therapeutic interventions have improved survivability, this malignancy remains the second leading cause of female cancer-related mortality. This sobering reality highlights an important shortfall in our current approach to breast cancer treatment, which is finding effective therapies for addressing metastatic disease, which is overwhelmingly responsible for the majority of breast cancer deaths. Therefore, this thesis aims to address this lingering issue by focusing on different ends of this deadly cascade. Specifically, in Chapter 1 I review the steps of the metastatic cascade and specific implications for breast cancer. In Chapter 2, I review what is currently known about nuclear receptor TLX (NR2E1), whose dysregulation, overexpression, or loss of expression has been characterized in numerous studies focused on a diverse range of pathological conditions, including cancer. Several studies have described putative synthetic and natural TLX ligands, suggesting that this receptor may serve as a therapeutic target. In Chapter 3, I present data demonstrating that elevated expression of TLX is a positive prognostic indicator in patients with ERα-negative and basal breast cancers, which is further supported by in vitro and in vivo analyses showing that TLX transcriptional regulation impedes the migratory and invasive capacity of triple-negative breast cancer cells. While this addresses the earlier phases of the metastatic cascade, Chapter 4 focuses on a later stage, examining how consumption of fried high-cholesterol food, and alterations to the immune population within the metastatic microenvironment, can promote the “awakening” of dormant tumor cells, one of the final phases of metastatic recurrence. Overall, this thesis takes a two-pronged approach to addressing breast cancer metastasis, providing data that could be used for future therapeutic development as well as lifestyle modification among breast cancer survivors.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular & Integrative Physi

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Nelczyk, Adam Tyler

Contributors dc:contributor

• Nelson, Erik R
• Katzenellenbogen, Benita
• Spinella, Michael J
• Madak-Erdogan, Zeynep

• Nuclear Receptor
• Tlx
• Nr2e1
• Breast Cancer
• Metastasis
• Tumor Dormancy
• High-cholesterol
• Cured
• Fried
• Bacon
• Histamines
• Mast Cells

Statement dc:rights

• Copyright 2022 Adam Nelczyk

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117554

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117554