Role of autotaxin and lysophosphatidate in cancer progression and resistance to chemotherapy and radiotherapy

Bibliography

• Samadi N, Bekele R, Capatos D, Venkatraman G, Sariahmetoglu M, Brindley DN. Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. Biochimie 93, 61–70 (2011)
   Google Scholar
• Yang SY, Lee J, Park CG et al. Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clin. Exp. Metastasis 19, 603–608 (2002)
   Google Scholar
• Nam SW, Clair T, Campo CK, Lee HY, Liotta LA, Stracke ML. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 19, 241–247 (2000)
   Google Scholar
• Nam SW, Clair T, Kim YS et al. Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res. 61, 6938–6944 (2001)
   Google Scholar
• Hama K, Aoki J, Fukaya M et al. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J. Biol. Chem. 279, 17634–17639 (2004)
   Google Scholar
• Umezu-Goto M, Kishi Y, Taira A et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J. Cell Biol. 158, 227–233 (2002). nn Together with [8], first identified autotaxin (ATX) as the lysophospholipase D activity that converted lysophosphatidylcholine to lysophosphatidate (LPA)
   Google Scholar
• Stracke ML, Krutzsch HC, Unsworth EJ et al. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J. Biol. Chem. 267, 2524–2529 (1992)
   Google Scholar
• Tokumura A, Majima E, Kariya Y et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J. Biol. Chem. 277, 39436–39442 (2002). nn Together with [6], first identified ATX as the lysophospholipase D activity that converted lysophosphatidylcholine to LPA
   Google Scholar
• An S, Dickens MA, Bleu T, Hallmark OG, Goetzl EJ. Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid. Biochem. Biophys. Res. Commun. 231, 619–622 (1997)
   Google Scholar
• Lee CW, Rivera R, Dubin AE, Chun J. LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation. J. Biol. Chem. 282, 4310–4317 (2007)
   Google Scholar
• Pasternack SM, von Kugelgen I, Aboud KA et al. G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat. Genet. 40, 329–334 (2008)
   Google Scholar
• Williams JR, Khandoga AL, Goyal P et al. Unique ligand selectivity of the GPR92/ LPA5 lysophosphatidate receptor indicates role in human platelet activation. J. Biol. Chem. 284, 17304–17319 (2009)
   Google Scholar
• Yanagida K, Ishii S. Non-Edg family LPA receptors: the cutting edge of LPA research. J. Biochem. 150, 223–232 (2011)
   Google Scholar
• Zhang Y, Scoumanne A, Chen X. G protein-coupled receptor 87: a promising opportunity for cancer drug discovery. Mol. Cell. Pharmacol. 2, 111–116 (2010)
   Google Scholar
• Murakami M, Shiraishi A, Tabata K, Fujita N. Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor. Biochem. Biophys. Res. Commun. 371, 707–712 (2008)
   Google Scholar
• Tanaka M, Okudaira S, Kishi Y et al. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J. Biol. Chem. 281, 25822–25830 (2006)
   Google Scholar
• Brindley DN. Lipid phosphate phosphatases and related proteins: signaling functions in development, cell division, and cancer. J. Cell. Biochem. 92, 900–912 (2004)
   Google Scholar
• Dennis J, Nogaroli L, Fuss B. Phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX): a multifunctional protein involved in central nervous system development and disease. J. Neurosci. Res. 82, 737–742 (2005)
   Google Scholar
• Fox MA, Alexander JK, Afshari FS, Colello RJ, Fuss B. Phosphodiesterase-I alpha/autotaxin controls cytoskeletal organization and FAK phosphorylation during myelination. Mol. Cell. Neurosci. 27, 140–150 (2004)
   Google Scholar
• Moolenaar WH, van Meeteren LA, Giepmans BN. The ins and outs of lysophosphatidic acid signaling. Bioessays 26, 870–881 (2004)
   Google Scholar
• Brindley DN. Hepatic secretion of lysphosphatidylcholine: a novel transport system for polyunsaturated fatty acids and choline. J. Nutr. Biochem. 4, 442–449 (1993)
   Google Scholar
• Aoki J, Taira A, Takanezawa Y et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J. Biol. Chem. 277, 48737–48744 (2002)
   Google Scholar
• Ferry G, Moulharat N, Pradere JP et al. S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool. J. Pharmacol. Exp. Ther. 327, 809–819 (2008)
   Google Scholar
• Albers HM, Dong A, van Meeteren LA et al. Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation. Proc. Natl Acad. Sci. USA 107, 7257–7262 (2010)
   Google Scholar
• Gierse J, Thorarensen A, Beltey K et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J. Pharmacol. Exp. Ther. 334, 310–317 (2010)
   Google Scholar
• Parrill AL, Baker DL. Autotaxin inhibition: challenges and progress toward novel anti-cancer agents. Anticancer Agents Med. Chem. 8, 917–923 (2008)
   Google Scholar
• Jansen S, Andries M, Derua R, Waelkens E, Bollen M. Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasispromoting enzyme autotaxin. J. Biol. Chem. 284, 14296–14302 (2009)
   Google Scholar
• Fourcade O, Simon MF, Viode C et al. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80, 919–927 (1995)
   Google Scholar
• Zhao X, Wang D, Zhao Z et al. Caspase-3- dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells. J. Biol. Chem. 281, 29357–29368 (2006)
   Google Scholar
• Li H, Zhao Z, Wei G et al. Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development. FASEB J. 24(10), 4103–4116 (2010)
   Google Scholar
• Venkatraman G, Brindley DN. Lipid phosphate phosphatases: their role in lysolipid degradation and cell signaling. In: Lysolipid Receptors: Signaling and Biochemistry. Hla T, Spiegel S, Moolenaar W, Chun J (Eds). John Wiley and Sons Inc., NY, USA (2012) (In Press)
   Google Scholar
• Zhang QX, Pilquil CS, Dewald J, Berthiaume LG, Brindley DN. Identification of structurally important domains of lipid phosphate phosphatase-1: implications for its sites of action. Biochem. J. 345(Pt 2), 181–184 (2000)
   Google Scholar
• Jasinska R, Zhang QX, Pilquil C et al. Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters. Biochem. J. 340, 677–686 (1999). n First showed that LPP1 is an ectophosphatase that degrades extracellular lipid phosphates and thus attenuates their activation of cell signaling
   Google Scholar
• Tomsig JL, Snyder AH, Berdyshev EV et al. Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo. Biochem. J. 419, 611–618 (2009)
   Google Scholar
• Brindley DN, Pilquil C. Lipid phosphate phosphatases and signaling. J. Lipid Res. 50(Suppl.), S225–S230 (2009)
   Google Scholar
• Milstien S, Spiegel S. Targeting sphingosine- 1-phosphate: a novel avenue for cancer therapeutics. Cancer Cell 9, 148–150 (2006)
   Google Scholar
• Sukocheva O, Wang L, Verrier E, Vadas MA, Xia P. Restoring endocrine response in breast cancer cells by inhibition of the sphingosine kinase-1 signaling pathway. Endocrinology 150, 4484–4492 (2009)
   Google Scholar
• Martin A, Gomez-Munoz A, Waggoner DW, Stone JC, Brindley DN. Decreased activities of phosphatidate phosphohydrolase and phospholipase D in ras and tyrosine kinase ( fps) transformed fibroblasts. J. Biol. Chem. 268, 23924–23932 (1993)
   Google Scholar
• Imai A, Furui T, Tamaya T, Mills GB. A gonadotropin-releasing hormoneresponsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells. J. Clin. Endocrinol. Metab. 85, 3370–3375 (2000)
   Google Scholar
• Tanyi JL, Hasegawa Y, Lapushin R et al. Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. Clin. Cancer Res. 9, 3534–3545 (2003)
   Google Scholar
• Tanyi JL, Morris AJ, Wolf JK et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res. 63, 1073–1082 (2003)
   Google Scholar
• Boucharaba A, Serre CM, Guglielmi J, Bordet JC, Clezardin P, Peyruchaud O. The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases. Proc. Natl Acad. Sci. USA 103, 9643–9648 (2006)
   Google Scholar
• Barila D, Plateroti M, Nobili F et al. The Dri 42 gene, whose expression is up-regulated during epithelial differentiation, encodes a novel endoplasmic reticulum resident transmembrane protein. J. Biol. Chem. 271, 29928–29936 (1996)
   Google Scholar
• Kai M, Wada I, Imai S, Sakane F, Kanoh H. Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase. J. Biol. Chem. 272, 24572–24578 (1997)
   Google Scholar
• Pyne S, Kong KC, Darroch PI. Lysophosphatidic acid and sphingosine 1-phosphate biology: the role of lipid phosphate phosphatases. Semin. Cell Dev. Biol. 15, 491–501 (2004)
   Google Scholar
• Alderton F, Darroch P, Sambi B et al. G-protein-coupled receptor stimulation of the p42/p44 mitogen-activated protein kinase pathway is attenuated by lipid phosphate phosphatases 1, 1a, and 2 in human embryonic kidney 293 cells. J. Biol. Chem. 276, 13452–13460 (2001). n First to demonstrate that lipid phosphate phosphatases attenuate cell signaling downstream of the activation of cell surface receptors, for example by stimulation of the thrombin receptor
   Google Scholar
• Long JS, Yokoyama K, Tigyi G, Pyne NJ, Pyne S. Lipid phosphate phosphatase-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration. Biochem. J. 394, 495–500 (2006)
   Google Scholar
• Long J, Darroch P, Wan KF et al. Regulation of cell survival by lipid phosphate phosphatases involves the modulation of intracellular phosphatidic acid and sphingosine 1-phosphate pools. Biochem. J. 391, 25–32 (2005)
   Google Scholar
• Pilquil C, Dewald J, Cherney A et al. Lipid phosphate phosphatase-1 regulates lysophosphatidate-induced fibroblast migration by controlling phospholipase D2-dependent phosphatidate generation. J. Biol. Chem. 281, 38418–38429 (2006). n Showed that LPP1 decreased LPA-induced cell migration by attenuating the activation of PLD2
   Google Scholar
• Leung DW, Tompkins CK, White T. Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells. DNA Cell Biol. 17, 377–385 (1998)
   Google Scholar
• Garcia-Murillas I, Pettitt T, Macdonald E et al. lazaro encodes a lipid phosphate phosphohydrolase that regulates phosphatidylinositol turnover during Drosophila phototransduction. Neuron 49, 533–546 (2006)
   Google Scholar
• Yue J, Yokoyama K, Balazs L et al. Mice with transgenic overexpression of lipid phosphate phosphatase-1 display multiple organotypic deficits without alteration in circulating lysophosphatidate level. Cell. Signal. 16, 385–399 (2004)
   Google Scholar
• Sciorra VA, Morris AJ. Sequential actions of phospholipase D and phosphatidic acid phosphohydrolase 2b generate diglyceride in mammalian cells. Mol. Biol. Cell 10, 3863–3876 (1999)
   Google Scholar
• Pyne S, Long JS, Ktistakis NT, Pyne NJ. Lipid phosphate phosphatases and lipid phosphate signalling. Biochem. Soc. Trans. 33, 1370–1374 (2005)
   Google Scholar
• Martin A, Duffy PA, Liossis C et al. Increased concentrations of phosphatidate, diacylglycerol and ceramide in ras- and tyrosine kinase (fps)-transformed fibroblasts. Oncogene 14, 1571–1580 (1997)
   Google Scholar
• Brindley D, Pilquil C, Sariahmetoglu M, Reue K. Phosphatidate degradation: phosphatidate phosphatases (lipins) and lipid phosphate phosphatases. Biochim. Biophys. Acta 1791(9), 956–961 (2009)
   Google Scholar
• Morris KE, Schang LM, Brindley DN. Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts. J. Biol. Chem. 281, 9297–9306 (2006)
   Google Scholar
• Michaloglou C, Vredeveld LC, Soengas MS et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005)
   Google Scholar
• Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997)
   Google Scholar
• Zhang N, Sundberg JP, Gridley T. Mice mutant for Ppap2c, a homolog of the germ cell migration regulator wunen, are viable and fertile. Genesis 27, 137–140 (2000)
   Google Scholar
• Flanagan JM, Funes JM, Henderson S, Wild L, Carey N, Boshoff C. Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets. Mol. Cancer Ther. 8, 249–260 (2009)
   Google Scholar
• Mandala SM. Sphingosine-1-phosphate phosphatases. Prostaglandins Other Lipid Mediat. 64, 143–156 (2001)
   Google Scholar
• Moughal NA, Waters C, Sambi B, Pyne S, Pyne NJ. Nerve growth factor signaling involves interaction between the Trk A receptor and lysophosphatidate receptor 1 systems: nuclear translocation of the lysophosphatidate receptor 1 and Trk A receptors in pheochromocytoma 12 cells. Cell. Signal. 16, 127–136 (2004)
   Google Scholar
• Gobeil F Jr, Bernier SG, Vazquez-Tello A et al. Modulation of pro-inflammatory gene expression by nuclear lysophosphatidic acid receptor type-1. J. Biol. Chem. 278, 38875– 38883 (2003)
   Google Scholar
• McIntyre TM, Pontsler AV, Silva AR et al. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc. Natl Acad. Sci. USA 100, 131–136 (2003)
   Google Scholar
• Siess W, Tigyi G. Thrombogenic and atherogenic activities of lysophosphatidic acid. J. Cell. Biochem. 92, 1086–1094 (2004)
   Google Scholar
• Pettus BJ, Kitatani K, Chalfant CE et al. The coordination of prostaglandin E2 production by sphingosine-1-phosphate and ceramide-1-phosphate. Mol. Pharmacol. 68, 330–335 (2005)
   Google Scholar
• Maceyka M, Payne SG, Milstien S, Spiegel S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim. Biophys. Acta 1585, 193–201 (2002)
   Google Scholar
• Taghavi P, Verhoeven E, Jacobs JJ et al. In vitro genetic screen identifies a cooperative role for LPA signaling and c-Myc in cell transformation. Oncogene 27, 6806–6816 (2008)
   Google Scholar
• Hausmann J, Kamtekar S, Christodoulou E et al. Structural basis of substrate discrimination and integrin binding by autotaxin. Nat. Struct. Mol. Biol. 18, 198–204 (2011). n Demonstrated the first crystal structure of ATX and an integrin binding site
   Google Scholar
• Fulkerson Z, Wu T, Sunakura M, Vander Kooi C, Morris AJ, Smyth SS. Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells. J. Biol. Chem. 286(40), 34654–34663 (2011). n Established that the binding of ATX to integrins can locate ATX on the surface of cells and thus generate LPA in proximity to LPA receptors
   Google Scholar
• Moolenaar WH, Perrakis A. Insights into autotaxin: how to produce and present a lipid mediator. Nat. Rev. Mol. Cell Biol. 12, 674–679 (2011)
   Google Scholar
• Albelda SM, Mette SA, Elder DE et al. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 50, 6757–6764 (1990)
   Google Scholar
• Hsu MY, Shih DT, Meier FE et al. Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. Am. J. Pathol. 153, 1435–1442 (1998)
   Google Scholar
• Desgrosellier JS, Barnes LA, Shields DJ et al. An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nat. Med. 15, 1163–1169 (2009)
   Google Scholar
• Yuelling LM, Fuss B. Autotaxin (ATX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties. Biochim. Biophys. Acta 1781, 525–530 (2008)
   Google Scholar
• Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat. Rev. Cancer 3, 582–591 (2003)
   Google Scholar
• Ishii I, Fukushima N, Ye X, Chun J. Lysophospholipid receptors: signaling and biology. Annu. Rev. Biochem. 73, 321–354 (2004)
   Google Scholar
• Hecht JH, Weiner JA, Post SR, Chun J. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J. Cell Biol. 135, 1071–1083 (1996). nn Reported the identification of the first LPA receptor
   Google Scholar
• Fukushima N, Kimura Y, Chun J. A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Proc. Natl Acad. Sci. USA 95, 6151–6156 (1998)
   Google Scholar
• Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J. Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc. Natl Acad. Sci. USA 97, 13384–13389 (2000)
   Google Scholar
• Shin KJ, Kim YL, Lee S et al. Lysophosphatidic acid signaling through LPA receptor subtype 1 induces colony scattering of gastrointestinal cancer cells. J. Cancer Res. Clin. Oncol. 135, 45–52 (2009)
   Google Scholar
• An S, Bleu T, Hallmark OG, Goetzl EJ. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J. Biol. Chem. 273, 7906–7910 (1998)
   Google Scholar
• Contos JJ, Ishii I, Fukushima N et al. Characterization of lpa(2) (Edg4) and lpa(1)/ lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol. Cell. Biol. 22, 6921–6929 (2002)
   Google Scholar
• Oh YS, Jo NW, Choi JW et al. NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation. Mol. Cell. Biol. 24, 5069–5079 (2004)
   Google Scholar
• Lin FT, Lai YJ, Makarova N, Tigyi G, Lin WC. The lysophosphatidic acid 2 receptor mediates down-regulation of Siva-1 to promote cell survival. J. Biol. Chem. 282, 37759–37769 (2007)
   Google Scholar
• Bandoh K, Aoki J, Hosono H et al. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J. Biol. Chem. 274, 27776–27785 (1999)
   Google Scholar
• Ye X, Hama K, Contos JJ et al. LPA3- mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435, 104–108 (2005)
   Google Scholar
• Lee Z, Cheng CT, Zhang H et al. Role of LPA4/p2y9/GPR23 in negative regulation of cell motility. Mol. Biol. Cell 19, 5435–5445 (2008)
   Google Scholar
• Schulte KM, Beyer A, Kohrer K, Oberhauser S, Roher HD. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int. J. Cancer 92, 249–256 (2001)
   Google Scholar
• Horak CE, Mendoza A, Vega-Valle E et al. Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2. Cancer Res. 67, 11751–11759 (2007)
   Google Scholar
• Horak CE, Lee JH, Elkahloun AG et al. Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2. Cancer Res. 67, 7238–7246 (2007)
   Google Scholar
• Kitayama J, Shida D, Sako A et al. Overexpression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res. 6, R640–R646 (2004)
   Google Scholar
• Hu YL, Tee MK, Goetzl EJ et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J. Natl Cancer Inst. 93, 762–768 (2001)
   Google Scholar
• Liu S, Umezu-Goto M, Murph M et al. Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. Cancer Cell 15, 539–550 (2009). nn Established the role of ATX and LPA1, LPA2 and LPA3 receptors in producing breast cancers in vivo
   Google Scholar
• Imamura F, Horai T, Mukai M, Shinkai K, Sawada M, Akedo H. Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D. Biochem. Biophys. Res. Commun. 193, 497–503 (1993)
   Google Scholar
• Scott SA, Selvy PE, Buck JR et al. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat. Chem. Biol. 5, 108–117 (2009)
   Google Scholar
• Jeong KJ, Park SY, Cho KH et al. The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene doi:10.1038/onc.2011.595 (2012) (Epub ahead of print)
   Google Scholar
• Huang MC, Lee HY, Yeh CC, Kong Y, Zaloudek CJ, Goetzl EJ. Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2). Oncogene 23, 122–129 (2004)
   Google Scholar
• Fishman DA, Liu Y, Ellerbroek SM, Stack MS. Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res. 61, 3194–3199 (2001)
   Google Scholar
• Harma V, Knuuttila M, Virtanen J et al. Lysophosphatidic acid and sphingosine-1- phosphate promote morphogenesis and block invasion of prostate cancer cells in threedimensional organotypic models. Oncogene 31, 2075–2089 (2011)
   Google Scholar
• Dorfleutner A, Stehlik C, Zhang J, Gallick GE, Flynn DC. AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells. J. Cell. Physiol. 213, 740–749 (2007)
   Google Scholar
• Ha KS, Yeo EJ, Exton JH. Lysophosphatidic acid activation of phosphatidylcholinehydrolysing phospholipase D and actin polymerization by a pertussis toxin-sensitive mechanism. Biochem. J. 303(Pt 1), 55–59 (1994)
   Google Scholar
• Shida D, Fang X, Kordula T et al. Cross-talk between LPA1 and epidermal growth factor receptors mediates up-regulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion. Cancer Res. 68, 6569–6577 (2008)
   Google Scholar
• Fang X, Yu S, Bast RC et al. Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J. Biol. Chem. 279, 9653–9661 (2004)
   Google Scholar
• Benoy IH, Salgado R, Van Dam P et al. Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin. Cancer Res. 10, 7157–7162 (2004)
   Google Scholar
• Charles AG, Han TY, Liu YY, Hansen N, Giuliano AE, Cabot MC. Taxol-induced ceramide generation and apoptosis in human breast cancer cells. Cancer Chemother. Pharmacol. 47, 444–450 (2001)
   Google Scholar
• Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 22, 5897–5906 (2003)
   Google Scholar
• Modrak DE, Gold DV, Goldenberg DM. Sphingolipid targets in cancer therapy. Mol. Cancer Ther. 5, 200–208 (2006)
   Google Scholar
• Martinez R, Navarro R, Lacort M, Ruiz-Sanz JI, Ruiz-Larrea MB. Doxorubicin induces ceramide and diacylglycerol accumulation in rat hepatocytes through independent routes. Toxicol. Lett. 190, 86–90 (2009)
   Google Scholar
• Simstein R, Burow M, Parker A, Weldon C, Beckman B. Apoptosis, chemoresistance, and breast cancer: insights from the MCF-7 cell model system. Exp. Biol. Med. (Maywood) 228, 995–1003 (2003)
   Google Scholar
• Delpy E, Hatem SN, Andrieu N et al. Doxorubicin induces slow ceramide accumulation and late apoptosis in cultured adult rat ventricular myocytes. Cardiovasc. Res. 43, 398–407 (1999)
   Google Scholar
• Zhang J, Alter N, Reed JC, Borner C, Obeid LM, Hannun YA. Bcl-2 interrupts the ceramide-mediated pathway of cell death. Proc. Natl Acad. Sci. USA 93, 5325–5328 (1996)
   Google Scholar
• Huang WC, Chen CL, Lin YS, Lin CF. Apoptotic sphingolipid ceramide in cancer therapy. J. Lipids 2011, 565316 (2011)
   Google Scholar
• Parra V, Eisner V, Chiong M et al. Changes in mitochondrial dynamics during ceramideinduced cardiomyocyte early apoptosis. Cardiovasc. Res. 77, 387–397 (2008)
   Google Scholar
• Samadi N, Gaetano C, Goping IS, Brindley DN. Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis. Oncogene 28, 1028–1039 (2009)
   Google Scholar
• Gómez-Muñoz A, Martin A, O'Brien L, Brindley DN. Cell-permeable ceramides inhibit the stimulation of DNA synthesis and phospholipase D activity by phosphatidate and lysophosphatidate in rat fibroblasts. J. Biol. Chem. 269, 8937–8943 (1994)
   Google Scholar
• Gómez-Muñoz A, Waggoner DW, O'Brien L, Brindley DN. Interaction of ceramides, sphingosine, and sphingosine 1-phosphate in regulating DNA synthesis and phospholipase D activity. J. Biol. Chem. 270, 26318–26325 (1995)
   Google Scholar
• Singh IN, Stromberg LM, Bourgoin SG, Sciorra VA, Morris AJ, Brindley DN. Ceramide inhibition of mammalian phospholipase D1 and D2 activities is antagonized by phosphatidylinositol 4,5-bisphosphate. Biochemistry 40, 11227–11233 (2001)
   Google Scholar
• Abousalham A, Liossis C, O'Brien L, Brindley DN. Cell-permeable ceramides prevent the activation of phospholipase D by ADP-ribosylation factor and RhoA. J. Biol. Chem. 272, 1069–1075 (1997)
   Google Scholar
• Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr. Drug Targets 9, 662–673 (2008)
   Google Scholar
• Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat. Rev. Cancer 10, 489–503 (2010)
   Google Scholar
• Sukocheva O, Wadham C, Holmes A et al. Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: the role of sphingosine kinase-1. J. Cell Biol. 173, 301–310 (2006)
   Google Scholar
• Sukocheva O, Wadham C, Xia P. Role of sphingolipids in the cytoplasmic signaling of estrogens. Steroids 74, 562–567 (2009)
   Google Scholar
• Sukocheva OA, Wang L, Albanese N, Pitson SM, Vadas MA, Xia P. Sphingosine kinase transmits estrogen signaling in human breast cancer cells. Mol. Endocrinol. 17, 2002–2012 (2003)
   Google Scholar
• Sukocheva OA, Yang Y, Gierthy JF. Estrogen and progesterone interactive effects in postconfluent MCF-7 cell culture. Steroids 74, 410–418 (2009)
   Google Scholar
• Takabe K, Kim RH, Allegood JC et al. Estradiol induces export of sphingosine 1-phosphate from breast cancer cells via ABCC1 and ABCG2. J. Biol. Chem. 285, 10477–10486 (2010)
   Google Scholar
• Delon C, Manifava M, Wood E et al. Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J. Biol. Chem. 279, 44763–44774 (2004)
   Google Scholar
• Murph MM, Hurst-Kennedy J, Newton V, Brindley DN, Radhakrishna H. Lysophosphatidic acid decreases the nuclear localization and cellular abundance of the p53 tumor suppressor in A549 lung carcinoma cells. Mol. Cancer Res. 5, 1201–1211 (2007)
   Google Scholar
• Zhang R, Wang J, Ma S, Huang Z, Zhang G. Requirement of Osteopontin in migration and the protection against Taxol-induced apoptosis via ATX-LPA axis in SGC7901 cells. BMC Cell Biol. 12, 11 (2011)
   Google Scholar
• Shuyu E, Lai YJ, Tsukahara R et al. Lysophosphatidic acid 2 receptor-mediated supramolecular complex formation regulates its antiapoptotic effect. J. Biol. Chem. 284, 14558–14571 (2009)
   Google Scholar
• Vidot S, Witham J, Agarwal R et al. Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. Cell. Signal. 22, 926–935 (2010)
   Google Scholar
• Deng W, Shuyu E, Tsukahara R et al. The lysophosphatidic acid type 2 receptor is required for protection against radiation-induced intestinal injury. Gastroenterology 132, 1834–1851 (2007). n Established that activation of LPA2 receptors protects cells against radiation-induced damage
   Google Scholar
• So J, Wang FQ, Navari J, Schreher J, Fishman DA. LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2 (VEGF-R2). Gynecol. Oncol. 97, 870–878 (2005)
   Google Scholar
• Ptaszynska MM, Pendrak ML, Stracke ML, Roberts DD. Autotaxin signaling via lysophosphatidic acid receptors contributes to vascular endothelial growth factorinduced endothelial cell migration. Mol. Cancer Res. 8, 309–321 (2010)
   Google Scholar
• Ptaszynska MM, Pendrak ML, Bandle RW, Stracke ML, Roberts DD. Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells. Mol. Cancer Res. 6, 352–363 (2008)
   Google Scholar
• Albers HM, Ovaa H. Chemical evolution of autotaxin inhibitors. Chem. Rev. 112(5), 2593–2603 (2012)
   Google Scholar
• Zhang H, Xu X, Gajewiak J et al. Dual activity lysophosphatidic acid receptor pan-antagonist/ autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res. 69, 5441–5449 (2009)
   Google Scholar
• Parrill AL, Baker DL. Autotaxin inhibitors: a perspective on initial medicinal chemistry efforts. Expert Opin Ther. Pat. 20, 1619–1625 (2010)
   Google Scholar
• Saunders LP, Ouellette A, Bandle R et al. Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion. Mol. Cancer Ther. 7, 3352–3362 (2008)
   Google Scholar
• Gupte R, Patil R, Liu J et al. Benzyl and naphthalene methylphosphonic acid inhibitors of autotaxin with anti-invasive and antimetastatic activity. ChemMedChem 6, 922–935 (2011)
   Google Scholar
• Swaney JS, Chapman C, Correa LD et al. A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br. J. Pharmacol. 160, 1699–1713 (2010).
   Google Scholar