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

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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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Acknowledgment

This work was supported by grants from the United States National Institutes of Health (KVH [1R01 CA114051-01A1]), and National Health and Medical Research Council of Australia (AWA[512154]). The work was also supported by a Biomedical Career Development Award from the National Health and Medical Research Council of Australia (AWA [402847]).

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Ekambaram, P., Lambiv, W., Cazzolli, R. et al. The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis. Cancer Metastasis Rev 30, 397–408 (2011). https://doi.org/10.1007/s10555-011-9297-9

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