GSBS Dissertations and Theses

ORCID ID

0000-0001-9863-4877

Publication Date

2017-12-12

Document Type

Doctoral Dissertation

Academic Program

Cell Biology

Department

Cell Biology

First Thesis Advisor

Gary Stein

Keywords

Runx1, Breast Cancer, Epithelial to Mesenchymal Transition (EMT), Cancer Stem Cell

Abstract

Breast cancer remains the most common malignant disease in women worldwide. Despite the advantages of early detection and improved treatments, studies into the mechanisms that initiate and drive breast cancer progression are still required. Recent studies have identified RUNX1, which is an essential transcription factor for hematopoiesis, is one of the most frequently mutated genes in breast cancer patients. However, the role of RUNX1 in the mammary gland is understudied.

In this dissertation, we examined the role of RUNX1 in both normal mammary epithelial and breast cancer cells. Our in vitro studies demonstrated that RUNX1 inhibits epithelial to mesenchymal transition (EMT), migration, and invasion, reflecting its tumor suppressor activity, which was confirmed in vivo. Moreover, RUNX1 also contributes significantly to inhibition of the phenotypes of breast cancer stem cells (CSC), which is responsible for metastasis and tumor relapse. We showed that Runx1 overexpression reduces the tumorsphere formation and cancer stem cell population. Overall, our studies provide mechanistic evidence for RUNX1 repression of EMT in mammary cells, anti-tumor activity in vivo and regulation of CSC-like properties in breast cancer.

Our results highlight crucial roles for RUNX1 in preventing epithelial to mesenchymal transition and tumor progression in breast cancer. This RUNX1 mediated mechanism points to novel intervention strategies for early stage breast cancer.

DOI

10.13028/M21Q2F

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Available for download on Thursday, January 24, 2019

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