Publication Date

5-2017

Date of Final Oral Examination (Defense)

4-14-2017

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biology

Major Advisor

Cheryl Jorcyk, Ph.D.

Advisor

Julia Thom Oxford, Ph.D.

Advisor

Kenneth A. Cornell, Ph.D.

Advisor

Daniel Fologea, Ph.D.

Advisor

Grant Trobridge, Ph.D.

Abstract

The process of breast tumor metastasis has been examined to a great extent in recent years, but connecting specific protein-protein interactions to respective metastatic events remains challenging. The primary cause of death in patients with breast cancer is not from the primary tumor itself but rather from tumor metastases, which cause over 90% of all mortalities. In order for tumor cells to metastasize, they must undergo a phenotypic change known as the epithelial-mesenchymal transition (EMT). An EMT allows for the intravasation of tumor cells into nearby blood vessels or lymphatic channels. Once the primary tumor cells are within the network of vessels, they undergo a homing process to specific organs within the body. For breast cancer, secondary metastatic locations include the liver, brain, lung, and bone. It is known that signaling by proteins called cytokines influences breast tumor cells to adopt a more metastatic and aggressive phenotype. Cytokine signaling often changes protein functioning in the surrounding tumor environment and can lead to increased vasculature, which provides nutrients to a growing tumor, or phenotypic changes to individual cells on the invasive edge of a proliferating tumor. Transmembrane proteins, such as cluster of differentiation 44 (CD44), contribute to cell migration, cell detachment, and cellular docking during metastasis. The upregulation of CD44 expression by cytokine signaling is observed in less aggressive tumor cells, while more aggressive tumor cells constitutively express high basal levels of CD44. Both EMT and CD44 induced by cytokines are involved in metastasis during specifically timed events in the metastatic cascade.

Available for download on Wednesday, May 22, 2019

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