Rho GTPases are critical for the dynamic changes in cell shape and adhesion that drive cell migration. in tumor progression, especially tumor cell proliferation, migration, and invasion that are key steps in cancer progression. In addition, the regulation of neovascularization by Dimethyl 4-hydroxyisophthalate 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. Keywords:Thromboxane synthase, Thromboxane receptor, Cyclooxygenase, Cancer progression, Metastasis, Angiogenesis, Cell migration, Dimethyl 4-hydroxyisophthalate Apoptosis == 1 Introduction == Thromboxane A2(TXA2) was one of the first prostaglandins to be identified from washed platelets (in 1975) and has been widely implicated in a range of cardiovascular diseases, owing to its acute and chronic effects in promoting platelet aggregation, vasoconstriction, and proliferation [13]. TXA2is a biologically active metabolite of arachidonic acid (AA) formed by the action of TXA2synthase (TXA2S) on prostaglandin endoperoxide (PGH2) [1,4,5]. TXA2is highly unstable in aqueous solution, where it spontaneously hydrolyzes to the biologically inactive hemiacetal thromboxane B2(TXB2) with a half-life of 30 s [4]. Due to its short half-life, TXA2primarily functions as an autocrine or paracrine mediator in the tissues surrounding its site of production. TXA2is responsible for multiple biological processes through the cell surface TXA2receptor, or T-prostanoid (TP) receptor [6,7]. TXA2biosynthesis and TP expression are elevated in numerous cardiovascular and inflammatory diseases [3,810]. It is felt that TXA2, through its receptors, plays a very important role in the pathogenesis of acute coronary artery syndrome, vessel remodeling, thrombosis, renal, pulmonary, and atherosclerotic cardiovascular diseases primarily through its action as a potent vasoconstrictor and an inducer of platelet aggregation and activation [8,9,1115]. As such TXA2S inhibition and hSPRY1 TP antagonism have become central to the therapy of many diseases including infarction, hypertension, stroke, and renal dysfunction [1618]. Recently a role for TXA2signaling in cancer has become apparent. This review will focus on some of the more recent findings and advances with a major emphasis on understanding the functional role of TXA2S and TP in cancer progression and metastasis. == 1.1 Thromboxane A2synthase == The cyclooxygenase enzymes, cyclooxygenase (COX)-1 and COX-2, are responsible for the conversion of AA to PGH2, the first step in the generation of TXA2. TXA2S is Dimethyl 4-hydroxyisophthalate an endoplasmic reticulum membrane protein that belongs to the P450 epoxygenase family that Dimethyl 4-hydroxyisophthalate catalyzes the conversion of the COX product PGH2to TXA2[19] (Fig. 1). TXA2S was first found as a microsomal enzyme in platelets (60 kDa) and is highly expressed in lung, Dimethyl 4-hydroxyisophthalate platelets, kidney, stomach, duodenum, colon, and spleen [2022]. TXA2S expression is reported to be closely associated with cardiovascular, renal, and inflammatory diseases [21,23]. == Fig. 1. == Generation of the prostanoids through metabolism of arachidonic acid. Arachidonic acid can be metabolized into different bioactive lipids by one of three distinct signaling pathways; the cyclooxygenase (COX), the lipoxygenase, and the P-450 epoxygenase pathways. The COX-isoforms-COX-1 and COX-2 are responsible for the conversion of AA to PGH2, the first step in the generation of TXA2. Thromboxane synthase (TXA2S) then catalyzes the conversion of the COX product, PGH2to TXA2 == 1.2 Thromboxane A2receptor == TXA2is responsible for multiple biological processes through its cell surface receptor TP. Ligation of TP by TXA2activates multiple downstream pathways, including phospholipase C, and raises intracellular Ca2+levels leading to vasoconstriction and platelet aggregation [6,21]. The TXA2receptor (TP) is a typical G-protein-coupled receptor expressed as two different isoforms in humans TP-alpha (TP) and TP-beta (TP) [24,25]. These TP isoforms arise via alternate splicing of a single gene.