Document Type

Dissertation - Open Access

Award Date

2023

Degree Name

Doctor of Philosophy (PhD)

Department / School

Chemistry and Biochemistry

First Advisor

Matthew Miller

Abstract

Breast cancer is a major cause of death among women in European and North American countries, even with improved methods for diagnosis and therapy. The mortality of breast cancer is mainly due to the migration of the primary tumor to distinct sites in the body and is very common in triple negative breast cancer (TNBC). This type of breast cancer affects younger woman and has a high recurrence rate. Unfortunately, TNBC is extremely difficult to control because of the absence of specific targets for treatment. Therefore, our research aim is to discover new therapeutic targets and identify novel approaches for treatment of TNBC. In this study the isogenic Hs578T/Hs578Ts(i)8 cell model is used. This model consists of two cell lines: the Hs578T cells represent a primary tumor whereas the Hs578Ts(i)8 cells have undergone biochemical changes that makes it more migratory and invasive. This cell model allows studying breast cancer progression since it resembles breast cancer patients that show metastatic disease. The focus of this project is on cell-cell adhesion molecules (cadherins), and the novel receptor tyrosine kinase, Ryk, their interactions and spatiotemporal rearrangements. These molecules are studied using various techniques and methods such as behavioral assays, western blots, coimmunoprecipitation, and immunofluorescence microscopy. The results of our experiments have allowed for determining a role for N-cadherin and cadherin-11, their location, and potential connection with Ryk in invasive TNBC. In summary, this study provides novel valuable insights on the role of cadherins and Ryk in the progression of TNBC.

Library of Congress Subject Headings

Breast -- Cancer -- Treatment.
Cadherins.
Protein-tyrosine kinase -- Receptors.

Publisher

South Dakota State University

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Rights Statement

In Copyright