Publication Date

12-2025

Date of Final Oral Examination (Defense)

9-24-2025

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biological Sciences

Supervisory Committee Chair

Cheryl L. Jorcyk, Ph.D.

Supervisory Committee Member

Daniel Fologea, Ph.D.

Supervisory Committee Member

Javier Ochoa-Reparaz, Ph.D.

Supervisory Committee Member

Ken Cornell, 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 2025. 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. However, no studies are focused on identifying the differences between HER2 positive (HER2+) and HER2 negative (HER2-) breast cancer. Thus, we aim to fully elucidate the difference between OSM in HER2+ versus HER2- breast cancer. RNA-Sequencing analysis of OSM-treated human HER2+ and HER2- breast cancer cells demonstrated significant differences in gene expression between both cell types upon treatment with OSM, including increased ribosome biogenesis- and epithelial to mesenchymal transition-associated genes. Additionally, to explain the differences in gene expression, we sought to understand the mechanisms behind the increased OSM-mediated signaling that occurs in HER2-, but not in HER2+, breast cancer by investigating the overlapping pathways. This dissertation aims to elucidate the unique role OSM plays in HER2+ versus HER2- breast cancer at the molecular level and provide detailed information on which breast cancer patients (HER2+ or HER2-) will most benefit most from anti-OSM therapeutics.

Available for download on Wednesday, December 01, 2027

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