Graduate Defense: Cody Wolf

Dissertation Information

Title: Unique Oncostatin M Functions Within The Context Of Estrogen Receptor Positive Breast Cancer And Therapeutic Development
For Patients

Program: Doctor of Philosophy in Biomolecular Sciences

Advisor: Dr. Cheryl L. Jorcyk, Biological Sciences

Committee Members: Dr. Eric Hayden, Biological Sciences; Dr. Lisa Warner, Chemistry and Biochemistry and Dr. Matthew Ferguson,  Physics

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 deaths 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. Our laboratory has identified that 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 in 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 on 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 as well as evaluate a mechanism for STAT3/ER direct interaction that may alter gene expression. Additionally, we evaluated the role of a novel anti OSM therapeutic and its correlation with decreased metastasis. This collective 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.