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

Cathcart, Mary Clare, Reynolds, John V., O'Byrne, Kenneth J., & Pidgeon, Graham P. (2010) The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer. Biochimica et Biophysica Acta - Reviews on Cancer, 1805(2), pp. 153-166.

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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 anti-tumor, a pro-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 overexpression has been shown to be chemopreventive 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. © 2010 Elsevier B.V. All rights reserved.

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ID Code: 64855
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Cancer, Prostacyclin, Prostacyclin synthase, Thromboxane A2, Thromboxane synthase, 15 hydroxy 11alpha, 9alpha epoxymethanoprosta 5, 13 dienoic acid, 7 [3 [(4 phenylsemicarbazido)methyl] 7 oxabicyclo[2.2.1]hept 2 yl] 5 heptenoic acid, antineoplastic agent, arachidonic acid, bm 567, camptothecin, cisplatin, cyclic AMP dependent protein kinase, cyclooxygenase 2, cyclooxygenase 2 inhibitor, dalteparin, furegrelate, heparin, iloprost, low molecular weight heparin, mitogen activated protein kinase 1, mitogen activated protein kinase 3, mitogen activated protein kinase p38, ozagrel, paclitaxel, peroxisome proliferator activated receptor alpha, peroxisome proliferator activated receptor delta, peroxisome proliferator activated receptor gamma, thromboxane synthase inhibitor, unclassified drug, unindexed drug, warfarin, antineoplastic activity, apoptosis, arachidonic acid metabolism, asthma, blood clotting, breast cancer, cancer growth, cancer inhibition, cancer invasion, carcinogenesis, cell proliferation, cell survival, clinical trial, colorectal cancer, drug efficacy, drug potentiation, drug targeting, endometrium carcinoma, enzyme activation, enzyme activity, epigenetics, genetic predisposition, human, kidney carcinoma, lung adenocarcinoma, lung cancer, lung non small cell cancer, metastasis, nonhuman, pancreas cancer, priority journal, promoter region, prostate cancer, protein expression, protein function, review, signal transduction, stomach cancer, thyroid papillary carcinoma, tumor vascularization, venous thromboembolism, Animals, Cytochrome P-450 Enzyme System, Disease Progression, Humans, Intramolecular Oxidoreductases, Neoplasms, Thromboxane-A Synthase, Murinae
DOI: 10.1016/j.bbcan.2010.01.006
ISSN: 0304-419X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 Elsevier BV
Deposited On: 27 Nov 2013 07:46
Last Modified: 13 Mar 2014 01:19

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