The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis

P Ekambaram, W Lambiv, R Cazzolli… - Cancer and Metastasis …, 2011 - Springer
P Ekambaram, W Lambiv, R Cazzolli, AW Ashton, KV Honn
Cancer and Metastasis Reviews, 2011Springer
Abstract Thromboxane A 2 (TXA 2) is a biologically active metabolite of arachidonic acid
formed by the action of the terminal synthase, thromboxane A 2 synthase (TXA 2 S), on
prostaglandin endoperoxide (PGH 2). TXA 2 is responsible for multiple biological processes
through its cell surface receptor, the T-prostanoid (TP) receptor. Thromboxane A 2 synthase
and TP are the two necessary components for the functioning of this potent bioactive lipid.
Thromboxane A 2 is widely implicated in a range of cardiovascular diseases, owing to its …
Abstract
Thromboxane A2 (TXA2) is a biologically active metabolite of arachidonic acid formed by the action of the terminal synthase, thromboxane A2 synthase (TXA2S), on prostaglandin endoperoxide (PGH2). TXA2 is responsible for multiple biological processes through its cell surface receptor, the T-prostanoid (TP) receptor. Thromboxane A2 synthase and TP are the two necessary components for the functioning of this potent bioactive lipid. Thromboxane A2 is widely implicated in a range of cardiovascular diseases, owing to its acute and chronic effects in promoting platelet aggregation, vasoconstriction, and proliferation. In recent years, additional functional roles for both TXA2S and TP in cancer progression have been indicated. Increased cyclooxygenase (COX)-2 expression has been described in a variety of human cancers, which has focused attention on TXA2 as a downstream metabolite of the COX-2-derived PGH2. Several studies suggest potential involvement of TXA2S and TP in tumor progression, especially tumor cell proliferation, migration, and invasion that are key steps in cancer progression. In addition, the regulation of neovascularization by TP has been identified as a potent source of control during oncogenesis. There have been several recent reviews of TXA2S and TP but thus far none have discussed its role in cancer progression and metastasis in depth. This review will focus on some of the more recent findings and advances with a significant emphasis on understanding the functional role of TXA2S and TP in cancer progression and metastasis.
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