Graduation Date

Fall 12-19-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Biochemistry & Molecular Biology

First Advisor

Melissa Teoh

Second Advisor

Sushil Kumar

Third Advisor

Rebecca Oberley-Deegan

Fourth Advisor

Parthasarathy Seshacharyulu

Abstract

Breast cancer is the second leading cause of cancer deaths in women in the United States. Frontline hormone therapies for breast cancer prove ineffective in triple negative breast cancer tumors wherein the hormones estrogen, progesterone, and HER2 are downregulated or absent; therefore, patients diagnosed with triple negative breast cancer are primarily limited to chemotherapies which carry a higher failure and resistance rate. Here we target cancer associated fibroblasts as potential drivers of chemoresistance in triple negative breast cancer. We investigated the mechanism by which Nox4 regulates the YAP/TAZ pathway in modulating DTX sensitivity and sought to determine if targeting Nox4 in TNBC cells will parallel the downregulation effects of the YAP/TAZ pathway as observed in CAFs. Our research involved the generation and manipulation of an immortalized mouse CAF line, and our results showed similarities in the results found in human breast cancer cells wherein Nox4 enhances YAP/TAZ-mediated paracrine signaling, thereby promoting a chemo-resistant tumor microenvironment, and that targeting Nox4-expressing CAFs will sensitize tumors to chemotherapy.

Comments

2025 Copyright, the authors

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