Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Moshmi Bhattacharya

Second Advisor

Dr. Andy Babwah

Third Advisor

Cindy Pape

Abstract

The lipid molecule lysophosphatidic acid (LPA) plays a critical role in cancer, stimulating cancer cell proliferation, survival, migration and invasion. Recently, LPA has been shown to enhance the metastasis of breast cancer cells to bone. However, the mechanisms by which LPA receptor signaling regulates cell migration and invasion of breast cancer cells were unclear and was the focus of this study. We show that breast cancer cell lines and tissue aberrantly express LPA receptors, β-arrestin, and Ral G proteins compared to normal mammry epithelial cells and tissue. Our studies provide strong evidence for LPAi receptor∕Gi⅛-signalιng as crucial mediators of LPA-induced breast cancer cell migration and invasion. Furthermore, our novel findings indicate a role for β-arrestin and Ral in regulating these processes and as potential therapeutic targets in the treatment of cancer.

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