Targeting Thromboxane A2 Receptor Signaling in Breast Cancer Metastasis

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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Campus Only Dissertation

Discipline thesis:degree_discipline

Molecular Biology, Microbiology and Biochemistry

Year

2012

Author dc:creator

• Zhang, Xuejing

Contributors dc:contributor

• Nie, Daotai

• breast cancer
• cytoskeleton
• G protein coupled receptor
• metastasis
• motility

Repository record dc:identifier

https://opensiuc.lib.siu.edu/dissertations/518

OAI identifier oai:identifier

oai:opensiuc.lib.siu.edu:dissertations-1518