Document Type

Thesis

Date of Award

5-2023

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

Committee Chairperson

Erica Cassimere

Committee Member 1

Mario Hollomon

Committee Member 2

Audrey Player

Committee Member 3

Dominique Guinn

Keywords

• Breast Cancer • Migration • Stem Cells

Abstract

Despite advances in treatment, breast cancer remains one of the leading causes of cancer deaths among women. Although early detection through mammograms and advances in treatments have shown great promise, tumor relapse still poses a major challenge. Breast cancer stem cells (CSCs) have been recently identified as a small subpopulation of breast cancer cells thought to promote breast cancer progression and drug resistance. Similar to normal stem cells, CSCs have the capacity for self-renewal, proliferation, and pluripotency. Breast CSCs also display increased cell migration and invasion. Therefore, targeting the growth of breast CSCs will provide novel strategies to combat breast cancer. p27Kip1 (p27), a member of the cyclin-dependent kinase inhibitor (CIP/KIP) family, mediates nuclear G1 cell cycle arrest with subsequent quiescence. p27 performs cell cycle-dependent and cell cycle-independent functions based on subcellular localization. Interestingly, cytoplasmic p27 displays CDK-independent functions, including enhanced cell migration and metastasis in a variety of solid tumors. Yet, the role for p27 in migration in breast CSCs has yet to be tested. We hypothesize that p27 increases the metastatic potential of breast cancer stem cells through increasing cell migration. This hypothesis is based on preliminary observations that revealed that p27 protein levels were markedly enhanced in CSCs isolated from metastatic breast cancer cell lines compared to those that were non-metastatic in nature. Using in vitro mammosphere assays, transwell cell migration assays and gene silencing, we found that p27 increased migratory populations from breast CSCs, suggesting that it could be an attractive target to combat breast cancer.

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