Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis

Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets

“…ATX-induced motility of melanoma cells is mediated through the activation of focal adhesion kinase (FAK) (Jung et al, 2004) and, in the nucleus, by the DNA binding of necrosis factor kappa B (NF-kB) (Lee et al, 2006). Another finding is that LPA strongly counteracts Taxol-induced death in the MCF-7 breast cancer cell line and in MDA-MB-435 melanoma cells, by activating phosphatidylinositol 3-kinase (PI3K), which antagonizes the Taxol-induced accumulation of cancer cells in the G2/M phase of the cell cycle (Samadi et al, 2009). Recently it has been demonstrated that the ATX/LPA axis allows breast cancer cells to escape from mitotic arrest following the PI3K-dependent displacement of Taxol from polymerised tubulin (Samadi et al, 2011).…”

“…Therefore, the identification of genes which confer drug resistance may offer novel therapeutic targets that can be exploited to develop drugs which re-sensitize tumour cells to chemotherapeutic agents (Richardson et al, 2005). ATX has been linked to chemoresistance due to its ability to inhibit apoptosis induced by paclitaxel in breast cancer cells (Samadi et al, 2009) and LPA can inhibit cell death induced by cisplatin (Frankel et al, 1996). It has been demonstrated that ATX may be a target for treating drug-resistant ovarian www.intechopen.com cancer.…”

Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo

“…LPA decreases the expression of the tumor suppressor p53 [67] , thus increasing cancer cell survival and division. We discovered that LPA produces resistance to the cytotoxic effects of paclitaxel, a first line treatment for breast cancer [9,15,68] . This was confirmed [69] and extended since LPA produces resistance to the apoptotic effects of carboplatin [70] and radiation-induced cell death [14][15]71] .…”

“…Historically, LPC was believed to be a bioactive molecule. However, more recent work has shown that ATX inhibition blocks the stimulatory effects of LPC on cell migration and survival [8][9] , demonstrating that the biological actions of LPC are mediated through LPA via ATX activity. LPA signaling is terminated by its hydrolysis to inorganic phosphate and monoacylglycerol (MAG) by catalytic activity of three related proteins called the lipid phosphate phosphatases (LPP1-3) (Fig.…”

Dendrimer Conjugate of [4-(Tetradecanoylamino)benzyl]phosphonic Acid (S32826) as an Autotaxin Inhibitor

“…LPA has previously been shown to inhibit cell death induced by cisplatin, 34 and autotaxin inhibits apoptosis induced by paclitaxel. 35 We have previously shown in cells engineered to overexpress autotaxin, that inhibition of autotaxin with the , n = 3−5, DMSO). * P < 0.05, ** P < 0.01, *** P < 0.001 denote results that differ significantly from vehicle alone (paired t test).…”