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

Nelczyk, Adam Tyler

Permalink

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

Description

Title

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

Author(s)

Nelczyk, Adam Tyler

Issue Date

2022-11-21

Director of Research (if dissertation) or Advisor (if thesis)

Nelson, Erik R

Doctoral Committee Chair(s)

Nelson, Erik R

Committee Member(s)

• Katzenellenbogen, Benita
• Spinella, Michael J
• Madak-Erdogan, Zeynep

Department of Study

Molecular & Integrative Physl

Discipline

Molecular & Integrative Physi

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Nuclear Receptor
• TLX
• NR2E1
• Breast Cancer
• Metastasis
• Tumor Dormancy
• High-Cholesterol
• Cured
• Fried
• Bacon
• Histamines
• Mast Cells

Abstract

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.

Graduation Semester

2022-12

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Adam Nelczyk

Owning Collections