Type

Journal Article

Authors

Ken O'Byrne
John Reynolds
Graham Pidgeon

Subjects

Pharmacology

Topics
cell survival cancer blood pressure prostacyclin synthase prostacyclin thromboxane a2 cell proliferation thromboxane synthase

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer (2010)

Abstract Prostacyclin synthase and thromboxane synthase signaling via arachidonic acid metabolism affects a number of tumor cell survival pathways such as cell proliferation, apoptosis, tumor cell invasion and metastasis, and angiogenesis. However, the effects of these respective synthases differ considerably with respect to the pathways described. While prostacyclin synthase is generally believed to be pro-tumor, an anti-carcinogenic role for thromboxane synthase has been demonstrated in a variety of cancers. The balance of oppositely acting COX-derived prostanoids influences many processes throughout the body, such as blood pressure regulation, clotting, and inflammation. The PGI2/TXA2 ratio is of particular interest in-vivo, with the corresponding synthases shown to be differentially regulated in a variety of disease states. Pharmacological inhibition of thromboxane synthase has been shown to significantly inhibit tumor cell growth, invasion, metastasis and angiogenesis in a range of experimental models. In direct contrast, prostacyclin synthase over-expression has been shown to be chemopreventative in a murine model of the disease, suggesting that the expression and activity of this enzyme may protect against tumor development. In this review, we discuss the aberrant expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. We discuss the effects of these enzymes on a range of tumor cell survival pathways, such as tumor cell proliferation, induction of apoptosis, invasion and metastasis, and tumor cell angiogenesis. As downstream signaling pathways of these enzymes have also been implicated in cancer states, we examine the role of downstream effectors of PGIS and TXS activity in tumor growth and progression. Finally, we discuss current therapeutic strategies aimed at targeting these enzymes for the prevention/treatment of cancer.
Collections Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> Surgery
Ireland -> Trinity College Dublin -> Surgery (Scholarly Publications)
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> School of Medicine

Full list of authors on original publication

Ken O'Byrne, John Reynolds, Graham Pidgeon

Experts in our system

1
Ken O'Byrne
Trinity College Dublin
Total Publications: 49
 
2
J V Reynolds
Trinity College Dublin
Total Publications: 206
 
3
Graham Pidgeon
Trinity College Dublin
Total Publications: 38