The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis.
The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis.
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DOI：
10.1007/s10555-011-9297-9
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发表时间：
2011-12
影响因子：
9.2
通讯作者：
Honn, Kenneth V.
中科院分区：
文献类型：
--
作者：
Ekambaram, Prasanna;Lambiv, Wanyu;Cazzolli, Rosanna;Ashton, Anthony W.;Honn, Kenneth V.
关键词：
血栓烷A2（TXA 2）是花生四烯酸的生物活性代谢产物，通过末端合酶血栓烷A2合酶（TXA 2S）作用于前列腺素内过氧化物（PGH 2）而形成。TXA 2通过其细胞表面受体T-前列腺素（TP）受体负责多种生物过程。血栓素A2合酶和TP是这种有效的生物活性脂质发挥功能的两个必要组分。血栓素A2由于其促进血小板聚集、血管收缩和增殖的急性和慢性作用而广泛涉及一系列心血管疾病。近年来，TXA 2S和TP在癌症进展中的额外功能作用已被指出。环氧化酶（考克斯）-2表达的增加已在多种人类癌症中被描述，其将注意力集中在作为考克斯-2衍生的PGH 2的下游代谢物的TXA 2上。一些研究表明，TXA 2S和TP可能参与肿瘤进展，特别是肿瘤细胞增殖、迁移和侵袭，这些是癌症进展的关键步骤。此外，TP对新血管形成的调节已被确定为肿瘤发生期间控制的有效来源。最近有几篇关于TXA 2S和TP的综述，但迄今为止还没有深入讨论其在癌症进展和转移中的作用。本文将重点介绍近年来的一些研究结果和进展，重点是了解TXA 2S和TP在癌症进展和转移中的功能作用。
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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