Date of Award

5-1-2012

Degree Name

Doctor of Philosophy

Department

Molecular Biology, Microbiology and Biochemistry

First Advisor

Nie, Daotai

Abstract

Breast cancer is the most common type of cancer among women in the United States and metastasis is the leading cause of mortality in patients diagnosed with malignant breast cancer. The receptor of thromboxane A2 (TxA2), TP, is a member of the G-protein coupled receptor family. Increased expression of TP at RNA level was found to correlate with a poor prognosis in breast cancer patients; however, it is unknown how TP expression and activities are involved in breast cancer progression. Here we report that TP is expressed in breast cancer cells at both RNA and protein levels. And further, activation of this receptor elicits rapid activation of small GTPase RhoA and cytoskeleton reorganization. We also found that knockdown of TP expression or inhibition of TP activation by SQ29548, a TP antagonist, reduces tumor cell motility, reduce tumor cell extravasation from the circulatory system, and most importantly, reduce breast cancer metastasis in vivo. These data provide compelling evidence suggesting that the TxA2-TP pathway plays an important role in breast cancer metastasis.

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