Date of Award
Spring 2025
Project Type
Dissertation
Program or Major
Biochemistry
Degree Name
Doctor of Philosophy
First Advisor
Sarah Walker
Second Advisor
Don Wojchowski
Third Advisor
Nate Oldenhuis
Abstract
Ovarian cancer is a disease often diagnosed in late stages and therefore is associated with metastasis. Ovarian cancer metastasis differs from other solid cancers as it does not primarily use the blood and lymph systems but often occurs throughout the peritoneal cavity. To do this, the ovarian cancer spheroids attach to and clear a layer of mesothelial cells in a process called mesothelial clearance. The initial process of clearing the layers has been shown to involve talin-1 and myosin-9 to physically push through the cell layer but few attempts have been taken to further understand the mechanism underlying clearance or to find substances to inhibit the ovarian cancer cells from promoting mesothelial clearance. Previous data from the Walker lab suggests that STAT3 plays a role in mesothelial clearance. Here we investigate STAT3’s effects on mesothelial clearance and use computational strategies to identify potential STAT3 inhibitors to prevent mesothelial clearance. We found that STAT3 inhibition downregulates genes in the cholesterol biosynthetic pathway which may prevent the synthesis of metabolites that are needed to anchor Rho, Rac and CDC42 to the membrane. We also provide evidence that the dysregulation or inhibition of Rho, Rac, and CDC42 are able to inhibit mesothelial clearance. These findings could provide a basis for therapeutic approaches in the future to minimize metastasis in ovarian cancer.
Recommended Citation
Reilly, Brendan Michael, "STAT3 and Mesothelial Clearance in Ovarian Cancer" (2025). Doctoral Dissertations. 2956.
https://scholars.unh.edu/dissertation/2956