Fol. Biol. 2023, 69, 149-162
https://doi.org/10.14712/fb2023069050149
Autotaxin and Lysophosphatidic Acid Signalling: the Pleiotropic Regulatory Network in Cancer
References
1. , H. M., Dong, A., van Meeteren, L. A. et al. (2010a) Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation. Proc. Natl. Acad. Sci. U. S. A. 107, 7257-7262.
<https://doi.org/10.1073/pnas.1001529107>
2. , H. M., van Meeteren, L. A., Egan, D. A. et al. (2010b) Discovery and optimization of boronic acid based inhibitors of autotaxin. J. Med. Chem. 53, 4958-4967.
<https://doi.org/10.1021/jm1005012>
3. , B., Chun, J. (2004) Cell surface receptors in lysophospholipid signaling. Semin. Cell Dev. Biol. 15, 457-465.
<https://doi.org/10.1016/j.semcdb.2004.05.005>
4. , J., Taira, A., Takanezawa, Y. et al. (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J. Biol. Chem. 277, 48737-48744.
<https://doi.org/10.1074/jbc.M206812200>
5. , D., Boulanger, M. C., Chignon, A. et al. (2019) Enhancer-mediated enrichment of interacting JMJD3-DDX21 to ENPP2 locus prevents R-loop formation and promotes transcription. Nucleic Acids Res. 47, 8424-8438.
<https://doi.org/10.1093/nar/gkz560>
6. , J., Doane, A., Leslie, K. et al. (2011) Stat3 mediates expression of autotaxin in breast cancer. PloS One 6, e27851.
<https://doi.org/10.1371/journal.pone.0027851>
7. , Z., Cai, L., Umemoto, E. et al. (2013) Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. J. Immunol. 190, 2036-2048.
<https://doi.org/10.4049/jimmunol.1202025>
8. , L., Okolicany, J., Ferrebee, M. et al. (2000) Topical application of LPA accelerates wound healing. Ann. N. Y. Acad. Sci. 905, 270-273.
<https://doi.org/10.1111/j.1749-6632.2000.tb06558.x>
9. , D. L., Fujiwara, Y., Pigg, K. R. et al. (2006) Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis. J. Biol. Chem. 281, 22786-22793.
<https://doi.org/10.1074/jbc.M512486200>
10. , S., Norman, D. D., Lee, S. C. et al. (2017) Highly potent non-carboxylic acid autotaxin inhibitors reduce melanoma metastasis and chemotherapeutic resistance of breast cancer stem cells. J. Med. Chem. 60, 1309-1324.
<https://doi.org/10.1021/acs.jmedchem.6b01270>
11. , E., Kaffe, E., Aidinis, V. et al. (2015) Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog. Lipid Res. 58, 76-96.
<https://doi.org/10.1016/j.plipres.2015.02.001>
12. , M. G., Tang, X., Maeda, T. et al. (2014) Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice. FASEB J. 28, 2655-2666.
<https://doi.org/10.1096/fj.13-248641>
13. , M. G., Tang, X., Dewald, J. et al. (2015a) Tumor-induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression. FASEB J. 29, 3990-4000.
<https://doi.org/10.1096/fj.15-274480>
14. , M. G., Zhao, Y. Y., Curtis, J. M. et al. (2015b) Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate. J. Lipid Res. 56, 1134-1144.
<https://doi.org/10.1194/jlr.M057661>
15. , M. G., Ko, Y. M., Tang, X. et al. (2015c) Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer. Endocr. Relat. Cancer 22, 593-607.
<https://doi.org/10.1530/ERC-15-0045>
16. , S. R., Dadey, D. Y., Karvas, R. M. et al. (2013) Autotaxin inhibition with PF-8380 enhances the radiosensitivity of human and murine glioblastoma cell lines. Front. Oncol. 3, 236.
<https://doi.org/10.3389/fonc.2013.00236>
17. , E., Tanfin, Z., Robin, P. (2008) Role of lysophosphatidic acid in the regulation of uterine leiomyoma cell proliferation by phospholipase D and autotaxin. J. Lipid Res. 49, 295-307.
<https://doi.org/10.1194/jlr.M700171-JLR200>
18. , A., Guillet, B., Menaa, F. et al. (2009) Bioactive lipids lysophosphatidic acid and sphingosine 1-phosphate mediate breast cancer cell biological functions through distinct mechanisms. Oncol. Res. 18, 173-184.
<https://doi.org/10.3727/096504009790217399>
19. , D. N., Lin, F. T., Tigyi, G. J. (2013) Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy. Biochim. Biophys. Acta 1831, 74-85.
<https://doi.org/10.1016/j.bbalip.2012.08.015>
20. , P., Walker, N. M., Braeuer, R. R. et al. (2020) Loss of FOXF1 expression promotes human lung-resident mesenchymal stromal cell migration via ATX/LPA/LPA1 signaling axis. Sci. Rep. 10, 21231.
<https://doi.org/10.1038/s41598-020-77601-1>
21. , M., Di Conza, G., Lahn, M. et al. (2023) Autotaxin inhibitor IOA-289 reduces gastrointestinal cancer progression in preclinical models. J. Exp. Clin. Cancer Res. 42, 197.
<https://doi.org/10.1186/s13046-023-02780-4>
22. , S., Marcoux, T. L., Deschęnes-Rompré, M. P. et al. (2015) Lysophosphatidic acid enhances collagen deposition and matrix thickening in engineered tissue. J. Tissue Eng. Regen. Med. 9, E65-E75.
<https://doi.org/10.1002/term.1711>
23. , M., O’Connor, K. L. (2005) Integrin α6β4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene 24, 5125-5130.
<https://doi.org/10.1038/sj.onc.1208729>
24. , J., Li, H., Xu, W. et al. (2021) Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer. BMC Gastroenterol. 21, 58.
<https://doi.org/10.1186/s12876-021-01635-6>
25. , J. W., Herr, D. R., Noguchi, K. et al. (2010) LPA receptors: subtypes and biological actions. Annu. Rev. Pharmacol. Toxicol. 50, 157-186.
<https://doi.org/10.1146/annurev.pharmtox.010909.105753>
26. , J. A., Kim, H., Kwon, H. et al. (2023) Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer. Br. J. Cancer 129, 1184-1194.
<https://doi.org/10.1038/s41416-023-02355-2>
27. , T., Lee, H. Y., Liotta, L. A. et al. (1997) Autotaxin is an exoenzyme possessing 5’-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J. Biol. Chem. 272, 996-1001.
<https://doi.org/10.1074/jbc.272.2.996>
28. , P., Andréasson, U., Kuci, V. et al. (2011) Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in vitro and more aggressive tumors in vivo. Mol. Oncol. 5, 527-537.
<https://doi.org/10.1016/j.molonc.2011.08.001>
29. , A. B., Wu, J., Lu, D. et al. (2007) Is autotaxin (ENPP2) the link between hepatitis C and hepatocellular cancer? J. Gastrointest. Surg. 11, 1628-1635.
<https://doi.org/10.1007/s11605-007-0322-9>
30. , W., Wang, F., He, L. et al. (2015) Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial-mesenchymal transition: partial mediation by the transcription factor NFAT1. Mol. Carcinog. 54, 301-311.
<https://doi.org/10.1002/mc.22100>
31. , M. A., Niewola-Staszkowska, K., Peyruchaud, O. et al. (2023) Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors. Immunooncol. Technol. 18, 100384.
<https://doi.org/10.1016/j.iotech.2023.100384>
32. , W., Wang, D. A., Gosmanova, E. et al. (2003) LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G821-G829.
<https://doi.org/10.1152/ajpgi.00406.2002>
33. , N., Housseman, C., Bock, X. et al. (2017) Discovery of 2-[[2-ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl] piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a first-in-class autotaxin inhibitor undergoing clinical evaluation for the treatment of idiopathic pulmonary fibrosis. J. Med. Chem. 60, 3580-3590.
<https://doi.org/10.1021/acs.jmedchem.7b00032>
34. , M. J., Humphreys, I. S., Rudge, S. A. et al. (2017) Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication. J. Hepatol. 66, 919-929.
<https://doi.org/10.1016/j.jhep.2017.01.009>
35. , G., Giganti, A., Cogé, F. et al. (2007) Functional invalidation of the autotaxin gene by a single amino acid mutation in mouse is lethal. FEBS Lett. 581, 3572-3578.
<https://doi.org/10.1016/j.febslet.2007.06.064>
36. , L., Jeong, K. J., Vellano, C. P. et al. (2016) Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression. J. Lipid Res. 57, 25-35.
<https://doi.org/10.1194/jlr.R060020>
37. , S., Oikonomou, N., Grigorieva, E. et al. (2010) ATX expression and LPA signalling are vital for the development of the nervous system. Dev. Biol. 339, 451-464.
<https://doi.org/10.1016/j.ydbio.2010.01.007>
38. , Z., Wu, T., Sunkara, M. et al. (2011) Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells. J. Biol. Chem. 286, 34654-34663.
<https://doi.org/10.1074/jbc.M111.276725>
39. , C. G., Samadi, N., Tomsig, J. L. et al. (2009) Inhibition of autotaxin production or activity blocks lysophosphatidylcholine-induced migration of human breast cancer and melanoma cells. Mol. Carcinog. 48, 801-809.
<https://doi.org/10.1002/mc.20524>
40. , J., Aksoy, B. A., Dogrusoz, U. et al. (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, pl1.
<https://doi.org/10.1126/scisignal.2004088>
41. S. N. (2009) Lysophosphatidic acid and autotaxin: emerging roles in innate and adaptive immunity. Immunol. Res. 45, 229-238.
<https://doi.org/10.1007/s12026-009-8104-y>
42. , J., Thorarensen, A., Beltey, K. et al. (2010) A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J. Pharmacol. Exp. Ther. 334, 310-317.
<https://doi.org/10.1124/jpet.110.165845>
43. , A., Rodriguez, M., Fould, B. et al. (2008) Murine and human autotaxin α, β, and γ isoforms: gene organization, tissue distribution, and biochemical characterization. J. Biol. Chem. 283, 7776-7789.
<https://doi.org/10.1074/jbc.M708705200>
44. , R., Ceulemans, H., Stalmans, W. et al. (2001) Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases. J. Biol. Chem. 276, 1361-1368.
<https://doi.org/10.1074/jbc.M007552200>
45. , J. W., Grobben, B., Slegers, H. (2003) Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim. Biophys. Acta 1638, 1-19.
<https://doi.org/10.1016/S0925-4439(03)00058-9>
46. , E. J., An, S. (1999) A subfamily of G protein-coupled cellular receptors for lysophospholipids and lysosphingolipids. Adv. Exp. Med. Biol. 469, 259-264.
<https://doi.org/10.1007/978-1-4615-4793-8_38>
47. , D., Weinberg, R. A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674.
<https://doi.org/10.1016/j.cell.2011.02.013>
48. , T., Okudaira, S., Igarashi, K. et al. (2012) Identification and biochemical characterization of a novel autotaxin isoform, ATXδ, with a four-amino acid deletion. J. Biochem. 151, 89-97.
<https://doi.org/10.1093/jb/mvr126>
49. , S., Mikami, S., Sugino, H. et al. (2016) Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer. Nat. Commun. 7, 10656.
<https://doi.org/10.1038/ncomms10656>
50. , J., Kamtekar, S., Christodoulou, E. et al. (2011) Structural basis of substrate discrimination and integrin binding by autotaxin. Nat. Struct. Mol. Biol. 18, 198-204.
<https://doi.org/10.1038/nsmb.1980>
51. , L., Yang, Y., Chen, J. et al. (2021) Transcriptional activation of ENPP2 by FoxO4 protects cardiomyocytes from doxorubicin‑induced toxicity. Mol. Med. Rep. 24, 668.
<https://doi.org/10.3892/mmr.2021.12307>
52. , D. B., Mariani, L., Weis, J. et al. (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7, 7-16.
<https://doi.org/10.1593/neo.04535>
53. , A. J., van Wijk, X. M., van Meeteren, L. A. et al. (2013) The polybasic insertion in autotaxin α confers specific binding to heparin and cell surface heparan sulfate proteoglycans. J. Biol. Chem. 288, 510-519.
<https://doi.org/10.1074/jbc.M112.358416>
54. , S., Hirane, M., Fukushima, K. et al. (2015) Diverse effects of LPA4, LPA5 and LPA6 on the activation of tumor progression in pancreatic cancer cells. Biochem. Biophys. Res. Commun. 461, 59-64.
<https://doi.org/10.1016/j.bbrc.2015.03.169>
55. , M. C., Zhang, D. D. (2013) The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 27, 2179-2191.
<https://doi.org/10.1101/gad.225680.113>
56. , S., Stefan, C., Creemers, J. W. et al. (2005) Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D. J. Cell Sci. 118(Pt 14), 3081-3089.
<https://doi.org/10.1242/jcs.02438>
57. , S., Callewaert, N., Dewerte, I. et al. (2007) An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D. J. Biol. Chem. 282, 11084-11091.
<https://doi.org/10.1074/jbc.M611503200>
58. , S., Andries, M., Derua, R. et al. (2009) Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasis-promoting enzyme autotaxin. J. Biol. Chem. 284, 14296-14302.
<https://doi.org/10.1074/jbc.M900790200>
59. , M., Matas-Rico, E., Rzadkowski, A. et al. (2011) LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor. PloS One 6, e29260.
<https://doi.org/10.1371/journal.pone.0029260>
60. , A., Kienesberger, P. C. (2021) Autotaxin-LPA-LPP3 axis in energy metabolism and metabolic disease. Int. J. Mol Sci. 22, 9575.
<https://doi.org/10.3390/ijms22179575>
61. , E., Katsifa, A., Xylourgidis, N. et al. (2017) Hepatocyte autotaxin expression promotes liver fibrosis and cancer. Hepatology 65, 1369-1383.
<https://doi.org/10.1002/hep.28973>
62. , H., Newton, R., Klein, R. et al. (2008) Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs. Nat. Immunol. 9, 415-423.
<https://doi.org/10.1038/ni1573>
63. , Y. C., Kim, K. M., Lee, K. S. et al. (2004) Serum bioactive lysophospholipids prevent TRAIL-induced apoptosis via PI3K/Akt-dependent cFLIP expression and Bad phosphorylation. Cell Death Differ. 11, 1287-1298.
<https://doi.org/10.1038/sj.cdd.4401489>
64. , A., Kaffe, E., Nikolaidou-Katsaridou, N. et al. (2015) The bulk of autotaxin activity is dispensable for adult mouse life. PloS One 10, e0143083.
<https://doi.org/10.1371/journal.pone.0143083>
65. , A., Englert, N., Seifert, A. et al. (2004) Expression, regulation and function of autotaxin in thyroid carcinomas. Int. J. Cancer 109, 833-838.
<https://doi.org/10.1002/ijc.20022>
66. , Y., Okudaira, S., Tanaka, M. et al. (2006) Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J. Biol. Chem. 281, 17492-17500.
<https://doi.org/10.1074/jbc.M601803200>
67. , S., Georas, S. N. (2014) The autotaxin-LPA axis emerges as a novel regulator of lymphocyte homing and inflammation. J. Immunol. 192, 851-857.
<https://doi.org/10.4049/jimmunol.1302831>
68. , J. M., Rodriguez, B. L., Wu, H. et al. (2023) Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer. J. Clin. Invest. 133, e163128.
<https://doi.org/10.1172/JCI163128>
69. , M., Miyagaki, T., Miyagawa, T. et al. (2018) Association between serum autotaxin or phosphatidylserine-specific phospholipase A1 levels and melanoma. J. Dermatol. 45, 571-579.
<https://doi.org/10.1111/1346-8138.14278>
70. , R., Sahay, D., Houssin, A. et al. (2018) Autotaxin-β interaction with the cell surface via syndecan-4 impacts on cancer cell proliferation and metastasis. Oncotarget 9, 33170-33185.
<https://doi.org/10.18632/oncotarget.26039>
71. , H. Y., Murata, J., Clair, T. et al. (1996) Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. Biochem. Biophys. Res. Commun. 218, 714-719.
<https://doi.org/10.1006/bbrc.1996.0127>
72. , J., Jung, I. D., Nam, S. W. et al. (2001) Enzymatic activation of autotaxin by divalent cations without EF-hand loop region involvement. Biochem. Pharmacol. 62, 219-224.
<https://doi.org/10.1016/S0006-2952(01)00658-X>
73. , Z., Cheng, C. T., Zhang, H. et al. (2008) Role of LPA4/p2y9/GPR23 in negative regulation of cell motility. Mol. Biol. Cell 19, 5435-5445.
<https://doi.org/10.1091/mbc.e08-03-0316>
74. , S., Wang, B., Xu, Y. et al. (2011) Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis. Mol. Cancer 10, 18.
<https://doi.org/10.1186/1476-4598-10-18>
75. , H., Yue, R., Wei, B. et al. (2014) Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis. EMBO J. 33, 1383-1396.
<https://doi.org/10.15252/embj.201387594>
76. , H. Y., Oh, Y. S., Choi, J. W. et al. (2017) Blocking lysophosphatidic acid receptor 1 signaling inhibits diabetic nephropathy in db/db mice. Kidney Int. 91, 1362-1373.
<https://doi.org/10.1016/j.kint.2016.11.010>
77. , M. E., Herr, D. R., Chun, J. (2010) Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. Prostaglandins Other Lipid Mediat. 91, 130-138.
<https://doi.org/10.1016/j.prostaglandins.2009.02.002>
78. , K. H., Lee, S. C., Dacheux, M. A. et al. (2023) E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: repression by p53 in murine but not in human carcinomas. FASEB J. 37, e23058.
<https://doi.org/10.1096/fj.202300838R>
79. , S., Murph, M., Panupinthu, N. et al. (2009a) ATX-LPA receptor axis in inflammation and cancer. Cell Cycle 8, 3695-3701.
<https://doi.org/10.4161/cc.8.22.9937>
80. , S., Umezu-Goto, M., Murph, M. et al. (2009b) Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. Cancer Cell 15, 539-550.
<https://doi.org/10.1016/j.ccr.2009.03.027>
81. , C., Antonopoulou, G., Fanidis, D. et al. (2022) Lysophosphatidic acid is a proinflammatory stimulus of renal tubular epithelial cells. Int. J. Mol. Sci. 23, 7452.
<https://doi.org/10.3390/ijms23137452>
82. , T. M., van der Aar, E. M., van de Steen, O. et al. (2018) Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir. Med. 6, 627-635.
<https://doi.org/10.1016/S2213-2600(18)30181-4>
83. , E., Frijlink, E., van der Haar Ŕvila, I. et al. (2021) Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells. Cell Rep. 37, 110013.
<https://doi.org/10.1016/j.celrep.2021.110013>
84. , A., Nakamura, K., Izutsu, K. et al. (2008) Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma. Br. J. Haematol. 143, 60-70.
<https://doi.org/10.1111/j.1365-2141.2008.07325.x>
85. , A., Dituri, F., Lupo, L. et al. (2011) Tumor-secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts. Hepatology 54, 920-930.
<https://doi.org/10.1002/hep.24485>
86. , A., Schönauer, L. M., De Nola, R. et al. (2018) Autotaxin is a novel molecular identifier of type I endometrial cancer. Med. Oncol. 35, 157.
<https://doi.org/10.1007/s12032-018-1222-4>
87. , Y., Kang, S., Fishman, D. A. (2005) Lysophosphatidic acid inhibits anti-Fas-mediated apoptosis enhanced by actin depolymerization in epithelial ovarian cancer. FEBS Lett. 579, 1311-1319.
<https://doi.org/10.1016/j.febslet.2005.01.026>
88. , G., Tang, X., Yang, Z. et al. (2017) Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. FASEB J. 31, 4064-4077.
<https://doi.org/10.1096/fj.201700159R>
89. , G., Tang, X., Yang, Z. et al. (2019) Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in adipose tissue: implications for the metabolic syndrome and breast cancer. FASEB J. 33, 1899-1910.
<https://doi.org/10.1096/fj.201801226R>
90. , W. H., Perrakis, A. (2011) Insights into autotaxin: how to produce and present a lipid mediator. Nat. Rev. Mol. Cell Biol. 12, 674-679.
<https://doi.org/10.1038/nrm3188>
91. , J., Lee, H. Y., Clair, T. et al. (1994) cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J. Biol. Chem. 269, 30479-30484.
<https://doi.org/10.1016/S0021-9258(18)43838-0>
92. , M. M. (2019) MicroRNA regulation of the autotaxin-lysophosphatidic acid signaling axis. Cancers (Basel) 11, 1369.
<https://doi.org/10.3390/cancers11091369>
93. , Y., Ikeda, H., Nakamura, K. et al. (2011) Specific increase in serum autotaxin activity in patients with pancreatic cancer. Clin. Biochem. 44, 576-581.
<https://doi.org/10.1016/j.clinbiochem.2011.03.128>
94. , H., Okudaira, S., Hama, K. et al. (2011) Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. Nat. Struct. Mol. Biol. 18, 205-212.
<https://doi.org/10.1038/nsmb.1998>
95. , S., Nagasaki, M., Okudaira, S. et al. (2014) ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity. Diabetes 63, 4154-4164.
<https://doi.org/10.2337/db13-1694>
96. , M. A., Wu, X. X., Okazoe, H. et al. (2009) Expression of autotaxin and acylglycerol kinase in prostate cancer: association with cancer development and progression. Cancer Sci. 100, 1631-1638.
<https://doi.org/10.1111/j.1349-7006.2009.01234.x>
97. , S. K., Strauch, P., Fujiwara, Y. et al. (2013) Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression. Cancer Immunol. Res. 1, 245-255.
<https://doi.org/10.1158/2326-6066.CIR-13-0043-T>
98. , C., Steudel, C., Heiderich, C. et al. (2013) Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Exp. Hematol. 41, 444-461.e4.
<https://doi.org/10.1016/j.exphem.2013.01.007>
99. , M., Fanidis, D., Aidinis, V. et al. (2021) ENPP2 methylation in health and cancer. Int. J. Mol. Sci. 22, 11958.
<https://doi.org/10.3390/ijms222111958>
100. , M., Drosouni, A., Fanidis, D. et al. (2022) ENPP2 promoter methylation correlates with decreased gene expression in breast cancer: implementation as a liquid biopsy biomarker. Int. J. Mol. Sci. 23, 3717.
<https://doi.org/10.3390/ijms23073717>
101. , S. Y., Jeong, K. J., Panupinthu, N. et al. (2011) Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression. Oncogene 30, 1351-1359.
<https://doi.org/10.1038/onc.2010.517>
102. , A. D., Maurhofer, O., Beyoglu, D. et al. (2011) Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. Cancer Res. 71, 6590-6600.
<https://doi.org/10.1158/0008-5472.CAN-11-0885>
103. , B., Hayward, M. K., Weaver, V. M. (2020) Fibrosis and cancer: a strained relationship. Biochim. Biophys. Acta Rev. Cancer 1873, 188356.
<https://doi.org/10.1016/j.bbcan.2020.188356>
104. Pietrobono, S., Sabbadini, F., Bertolini, M. et al. (2023) Autotaxin secretion is a stromal mechanism of adaptive resistance to TGFβ inhibition in pancreatic ductal adenocarcinoma. Cancer Res. Online ahead.
<https://doi.org/10.1158/0008-5472.CAN-23-0104>
105. , J. P., Tarnus, E., Grès, S. et al. (2007) Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase. Biochim. Biophys. Acta 1771, 93-102.
<https://doi.org/10.1016/j.bbalip.2006.11.010>
106. , M. M., Pendrak, M. L., Stracke, M. L. et al. (2010) Autotaxin signaling via lysophosphatidic acid receptors contributes to vascular endothelial growth factor-induced endothelial cell migration. Mol. Cancer Res. 8, 309-321.
<https://doi.org/10.1158/1541-7786.MCR-09-0288>
107. , M., Long, Y., Wang, Y. et al. (2023) Hypoxia increases ATX expression by histone crotonylation in a HIF-2α-dependent manner. Int. J. Mol. Sci. 24, 7031.
<https://doi.org/10.3390/ijms24087031>
108. , R., Rai, V. (2017) Lysophosphatidic acid converts monocytes into macrophages in both mice and humans. Blood 129, 1177-1183.
<https://doi.org/10.1182/blood-2016-10-743757>
109. , C. M., Tucker, A. L., Lynch, K. R. (2008) Lysophosphatidic acid (LPA) and angiogenesis. Angiogenesis 11, 301-310.
<https://doi.org/10.1007/s10456-008-9113-5>
110. , R., Ghaleb, A., Shim, H. et al. (2007) Lysophosphatidic acid prevents apoptosis of Caco-2 colon cancer cells via activation of mitogen-activated protein kinase and phosphorylation of Bad. Biochim. Biophys. Acta 1770, 1194-1203.
<https://doi.org/10.1016/j.bbagen.2007.04.008>
111. , J. M., Han, H. J. (2015) Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3β/β-catenin and PKC/Rho GTPase pathways. Stem Cells 33, 819-832.
<https://doi.org/10.1002/stem.1882>
112. , H., Ohhata, A., Hayashi, A. et al. (2014) A novel highly potent autotaxin/ENPP2 inhibitor produces prolonged decreases in plasma lysophosphatidic acid formation in vivo and regulates urethral tension. PloS One 9, e93230.
<https://doi.org/10.1371/journal.pone.0093230>
113. , J. P., Hao, N. T. T., Han, X. et al. (2020) Ectonucleotide pyrophosphatase 2 (ENPP2) plays a crucial role in myogenic differentiation through the regulation by WNT/β-Catenin signaling. Int. J. Biochem. Cell Biol. 118, 105661.
<https://doi.org/10.1016/j.biocel.2019.105661>
114. , N., Bekele, R. T., Goping, I. S. et al. (2011) Lysophosphatidate induces chemo-resistance by releasing breast cancer cells from taxol-induced mitotic arrest. PloS One 6, e20608.
<https://doi.org/10.1371/journal.pone.0020608>
115. , Y., Ohkawa, R., Nakamura, K. et al. (2007) Lysophosphatidic acid protection against apoptosis in the human pre-B-cell line Nalm-6. Eur. J. Haematol. 78, 510-517.
<https://doi.org/10.1111/j.1600-0609.2007.00849.x>
116. , L. P., Ouellette, A., Bandle, R. et al. (2008) Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion. Mol. Cancer Ther. 7, 3352-3362.
<https://doi.org/10.1158/1535-7163.MCT-08-0463>
117. , L. P., Cao, W., Chang, W. C. et al. (2011) Kinetic analysis of autotaxin reveals substrate-specific catalytic pathways and a mechanism for lysophosphatidic acid distribution. J. Biol. Chem. 286, 30130-30141.
<https://doi.org/10.1074/jbc.M111.246884>
118. , I., Kaffe, E., Mouratis, M. A. et al. (2013) Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and ATX/LPA axes. Biochim. Biophys. Acta 1831, 42-60.
<https://doi.org/10.1016/j.bbalip.2012.07.019>
119. , B. H., Baukal, A. J., Shah, F. B. et al. (2005) Mechanisms of extracellularly regulated kinases 1/2 activation in adrenal glomerulosa cells by lysophosphatidic acid and epidermal growth factor. Mol. Endocrinol. 19, 2535-2548.
<https://doi.org/10.1210/me.2005-0082>
120. , Y., Yu, Y., He, Y. et al. (2019) Serum ATX as a novel biomarker for breast cancer. Medicine (Baltimore) 98, e14973.
<https://doi.org/10.1097/MD.0000000000014973>
121. , Z. C., Zhu, B. H., Huang, A. F. et al. (2022) Docosahexaenoic acid reverses epithelial-mesenchymal transition and drug resistance by impairing the PI3K/AKT/Nrf2/GPX4 signalling pathway in docetaxel-resistant PC3 prostate cancer cells. Folia Biol. (Praha) 68, 59-71.
<https://doi.org/10.14712/fb2022068020059>
122. , B. S., Tager, A. M. (2012) Role of the lysophospholipid mediators lysophosphatidic acid and sphingosine 1-phosphate in lung fibrosis. Proc. Am. Thorac. Soc. 9, 102-110.
<https://doi.org/10.1513/pats.201201-005AW>
123. , D., Watanabe, T., Aoki, J. et al. (2004) Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Lab. Invest. 84, 1352-1362.
<https://doi.org/10.1038/labinvest.3700146>
124. , S., Czaplinski, J., Hu, L. et al. (2014) c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas. J. Pathol. 234, 190-202.
<https://doi.org/10.1002/path.4379>
125. , J., Clair, T., Noh, J. H. et al. (2005) Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate. Biochem. Biophys. Res. Commun. 337, 967-975.
<https://doi.org/10.1016/j.bbrc.2005.09.140>
126. , M. J., Devitt, G., Brosius, M. et al. (2001) Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br. J. Cancer 85, 1372-1382.
<https://doi.org/10.1054/bjoc.2001.2074>
127. , C., Jansen, S., Bollen, M. (2005) NPP-type ectophosphodiesterases: unity in diversity. Trends Biochem. Sci. 30, 542-550.
<https://doi.org/10.1016/j.tibs.2005.08.005>
128. , M. L., Krutzsch, H. C., Unsworth, E. J. et al. (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J. Biol. Chem. 267, 2524-2529.
<https://doi.org/10.1016/S0021-9258(18)45911-X>
129. , Y., Yang, Y., Wang, J. et al. (2015) Lysophosphatidic acid inhibits apoptosis induced by cisplatin in cervical cancer cells. Biomed Res. Int. 2015, 598386.
<https://doi.org/10.1155/2015/598386>
130. , H., Ren, J., Zhu, Q. et al. (2009) Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action. World J. Gastroenterol. 15, 4547-4555.
<https://doi.org/10.3748/wjg.15.4547>
131. , S., Zhang, X., Lyu, L. et al. (2016) Autotaxin expression is regulated at the post-transcriptional level by the RNA-binding proteins HuR and AUF1. J. Biol. Chem. 291, 25823-25836.
<https://doi.org/10.1074/jbc.M116.756908>
132. , S., Wang, R., Song, J. et al. (2017) Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity. J. Lipid Res. 58, 2102-2113.
<https://doi.org/10.1194/jlr.M075655>
133. , K., Fukushima, K., Onishi, Y. et al. (2017) Lysophosphatidic acid (LPA) signaling via LPA4 and LPA6 negatively regulates cell motile activities of colon cancer cells. Biochem. Biophys. Res. Commun. 483, 652-657.
<https://doi.org/10.1016/j.bbrc.2016.12.088>
134. , A., Kobayashi, D., Aoi, K. et al. (2016) Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility. eLife 5, e10561.
<https://doi.org/10.7554/eLife.10561>
135. , M., Okudaira, S., Kishi, Y. et al. (2006) Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J. Biol. Chem. 281, 25822-25830.
<https://doi.org/10.1074/jbc.M605142200>
136. , X., Benesch, M. G., Brindley, D. N. (2015) Lipid phosphate phosphatases and their roles in mammalian physiology and pathology. J. Lipid Res. 56, 2048-2060.
<https://doi.org/10.1194/jlr.R058362>
137. , X., Wuest, M., Benesch, M. G. K. et al. (2020) Inhibition of autotaxin with GLPG1690 increases the efficacy of radiotherapy and chemotherapy in a mouse model of breast cancer. Mol. Cancer Ther. 19, 63-74.
<https://doi.org/10.1158/1535-7163.MCT-19-0386>
138. , X., Morris, A. J., Deken, M. A. et al. (2023) Autotaxin inhibition with IOA-289 decreases breast tumor growth in mice whereas knockout of autotaxin in adipocytes does not. Cancers (Basel) 15, 2937.
<https://doi.org/10.3390/cancers15112937>
139. , G. (2010) Aiming drug discovery at lysophosphatidic acid targets. Br. J. Pharmacol. 161, 241-270.
<https://doi.org/10.1111/j.1476-5381.2010.00815.x>
140. , A., Majima, E., Kariya, Y. et al. (2002) Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J. Biol. Chem. 277, 39436-39442.
<https://doi.org/10.1074/jbc.M205623200>
141. , A., Kume, T., Fukuzawa, K. et al. (2007) Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity. Life Sci. 80, 1641-1649.
<https://doi.org/10.1016/j.lfs.2006.12.041>
142. , T., Hirata, M., Takahashi, T. et al. (2001) A dual signaling cascade that regulates the ectodomain shedding of heparin-binding epidermal growth factor-like growth factor. J. Biol. Chem. 276, 30475-30482.
<https://doi.org/10.1074/jbc.M103673200>
143. , M., Kishi, Y., Taira, A. et al. (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J. Cell Biol. 158, 227-233.
<https://doi.org/10.1083/jcb.200204026>
144. , E. J., van Rijswijk, A., Jalink, K. et al. (1992) Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Dependence on acyl-chain length and inhibition by suramin. Biochem. J. 281(Pt 1), 163-169.
<https://doi.org/10.1042/bj2810163>
145. , L. A., Ruurs, P., Stortelers, C. et al. (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol. Cell. Biol. 26, 5015-5022.
<https://doi.org/10.1128/MCB.02419-05>
146. , G., Benesch, M. G., Tang, X. et al. (2015) Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes involved in drug resistance and oxidative stress responses: implications for cancer treatment. FASEB J. 29, 772-785.
<https://doi.org/10.1096/fj.14-262659>
147. , S., Witham, J., Agarwal, R. et al. (2010) Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. Cell. Signal. 22, 926-935.
<https://doi.org/10.1016/j.cellsig.2010.01.017>
148. , O., Talacko, P., Musil, Z. et al. (2023) Identification of potential molecular targets for the treatment of cluster 1 human pheochromocytoma and paraganglioma via comprehensive proteomic characterization. Clin. Proteomics 20, 39.
<https://doi.org/10.1186/s12014-023-09428-7>
149. , Y., Lyu, L., Zhang, X. et al. (2019) Autotaxin is a novel target of microRNA-101-3p. FEBS Open Bio 9, 707-716.
<https://doi.org/10.1002/2211-5463.12608>
150. , T. M., Williams, M. E., Kuick, R. et al. (2005) Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability. Dev. Biol. 279, 462-480.
<https://doi.org/10.1016/j.ydbio.2004.12.015>
151. , J. M., Xu, Y., Skill, N. J. et al. (2010) Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma. Mol. Cancer 9, 71.
<https://doi.org/10.1186/1476-4598-9-71>
152. , T., Kooi, C. V., Shah, P. et al. (2014) Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration. FASEB J. 28, 861-870.
<https://doi.org/10.1096/fj.13-232868>
153. , D., Yu, S., Li, L. et al. (2020) The FOXM1/ATX signaling contributes to pancreatic cancer development. Am. J. Transl. Res. 12, 4478-4487.
154. , Y., Fang, X. J., Casey, G. et al. (1995) Lysophospholipids activate ovarian and breast cancer cells. Biochem J. 309(Pt 3), 933-940.
<https://doi.org/10.1042/bj3090933>
155. , M. Y., Porte, J., Knox, A. J. et al. (2009) Lysophosphatidic acid induces αvβ6 integrin-mediated TGF-β activation via the LPA2 receptor and the small G protein Gαq. Am. J. Pathol. 174, 1264-1279.
<https://doi.org/10.2353/ajpath.2009.080160>
156. , A., Khan, A. K.., Chen, F. et al. (2016) Overexpression of autotaxin is associated with human renal cell carcinoma and bladder carcinoma and their progression. Med. Oncol. 33, 131.
<https://doi.org/10.1007/s12032-016-0836-7>
157. , X., Zhang, Y., Zhang, J. et al. (2020) NSun2 promotes cell migration through methylating autotaxin mRNA. J. Biol. Chem. 295, 18134-18147.
<https://doi.org/10.1074/jbc.RA119.012009>
158. , Y., Mou, L.-J., Liu, N. et al. (1999) Autotaxin expression in non-small-cell lung cancer. Am. J. Respir. Cell Mol. Biol. 21, 216-222.
<https://doi.org/10.1165/ajrcmb.21.2.3667>
159. , S., Murph, M. M., Lu, Y. et al. (2008) Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J. Natl. Cancer Inst. 100, 1630-1642.
<https://doi.org/10.1093/jnci/djn378>
160. , Y. C., Stoddard, N. C., Chun, J. (2014) LPA receptor signaling: pharmacology, physiology, and pathophysiology. J. Lipid Res. 55, 1192-1214.
<https://doi.org/10.1194/jlr.R046458>
161. , Y., Chen, Y. C., Krummel, M. F. et al. (2012) Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J. Immunol. 189, 3914-3924.
<https://doi.org/10.4049/jimmunol.1201604>
162. , R., Li, B., Huang, J. et al. (2017) Lysophosphatidic acid is a biomarker for peritoneal carcinomatosis of gastric cancer and correlates with poor prognosis. Genet. Test. Mol. Biomarkers 21, 641-648.
<https://doi.org/10.1089/gtmb.2017.0060>
163. , V., Sokolov, E., Swet, J. H. et al. (2016) Expression and function of lysophosphatidic acid receptors (LPARs) 1 and 3 in human hepatic cancer progenitor cells. Oncotarget 7, 2951-2967.
<https://doi.org/10.18632/oncotarget.6696>
164. , S., Mulholland, S., Adamali, H. et al. (2020) Inhibitors of the autotaxin-lysophosphatidic acid axis and their potential in the treatment of interstitial lung disease: current perspectives. Clin. Pharmacol. 12, 97-108.
