Date of Award

Spring 2025

Project Type

Thesis

Program or Major

Biochemistry

Degree Name

Master of Science

First Advisor

Sarah R Walker

Second Advisor

Sherine Elsawa

Third Advisor

Nathan Oldenhuis

Abstract

Cancers of the female reproductive system, including breast and ovarian cancers, remain significant health concerns today. Breast cancer, which impacts 1 in 8 women in the U.S., is the second most common cancer-related death in women and ovarian cancer remains the leading cause of gynecological cancer-related deaths in women. While these statistics highlight the concerning reality of the metastatic disease state, when detected in early stages both cancer types do show high survival rates. These cancers, like many others, rely on a few processes to metastasize to further areas of the body, providing potential therapeutic targets. Cell migration, invasion, and clearance are crucial to this process and have all been found to be associated with the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). To further understand the contributions of STAT3 to cell migration and metastatic pathways, we studied the effects of various inhibitors of the STAT3 pathway on the capabilities of both diseased and non-diseased models. We found that STAT3 is a critical component of the diseased models but has varying impacts on the migration and invasion of non-diseased mouse embryonic fibroblasts (MEF). While the role of STAT3 in migration is consistent with the breast and ovarian cancer models, it appears to be significantly less important in the invasive capabilities of MEFs. These findings suggested a potential compensatory mechanism responsible for the regulation of invasion of MEFs. Rac1 and NNMT were explored as potential mechanisms, though did not explain all aspects of these differences. Additionally, the non-nuclear roles of STAT3 were investigated to further understand their contributions to these overall processes. While the studies with mitochondrial STAT3 and focal adhesion kinases did not suggest large impacts on these processes, actin associated proteins may have a more significant role in migration and metastasis.

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