Publication Date

8-2024

Date of Final Oral Examination (Defense)

5-23-2024

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department Filter

Biology

Department

Biology

Supervisory Committee Chair

Cheryl L. Jorcyk, Ph.D.

Supervisory Committee Member

Eric J. Hayden, Ph.D.

Supervisory Committee Member

Lisa R. Warner, Ph.D.

Supervisory Committee Member

Matthew L. Ferguson, Ph.D.

Abstract

In the United States, it is estimated that over 295,000 women will be diagnosed with breast cancer, and over 43,000 breast cancer patients will die in 2024. Mortality in breast cancer is due in large part due to distant metastasis to organs such as the bone, lung, liver, and brain. The IL-6-family cytokine oncostatin M (OSM) plays a crucial role in initiating metastasis by secreting pro-metastatic molecules such as VEGF, LOXL2 and IL-6, and increasing circulating tumor cell numbers and metastases to lung in vivo. More recent work within our lab has identified unique roles for OSM within the varying subtypes of breast cancer patients, particularly between estrogen receptor positive (ER+) and ER- patients. It is well known that patients with ER- breast cancer, specifically triple negative breast cancer (TNBC; ER- PR- HER2-), have limited therapeutic options. However, the divergent role OSM plays in ER+ and ER- breast cancer and the mechanism by which this occurs has yet to be fully understood. Thus, we aimed to fully elucidate the difference between OSM in ER+ versus ER- breast cancer. RNA-Sequencing analysis of OSM-treated human ER+ cells and ER- TNBC cells discovered significant differences in gene expression between both cell lines upon treatment with OSM, including alteration in DNA-replication and cell cycle pathway genes. Additionally, we sought to understand the mechanism behind which OSM-mediated signaling occurs in ER+ breast cancer through identifying a possible physical interaction between STAT3 and ER that could ultimately alter gene expression. Finally, we evaluated the role of a novel anti-OSM therapeutic and its correlation with decreased metastasis in ER+ breast cancer. This dissertation aims to elucidate the unique role OSM plays in ER+ and ER- breast cancer and will provide a molecular understanding of how this occurs and will provide detailed information on which patients will benefit most from anti-OSM therapeutics.

Comments

https://orcid.org/0000-0002-4769-9571

DOI

https://doi.org/10.18122/td.2280.boisestate

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