Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development

Lysophosphatidic acid (LPA) is a ubiquitous lysophospholipid and one of the main membrane-derived lipid signaling molecules. LPA acts as an autocrine/paracrine messenger through at least six G protein-coupled receptors (GPCRs), known as LPA1–6, to induce various cellular processes including wound healing, differentiation, proliferation, migration, and survival. LPA receptors and autotaxin (ATX), a secreted phosphodiesterase that produces this phospholipid, are overexpressed in many cancers and impact several features of the disease, including cancer-related inflammation, development, and progression. Many ongoing studies aim to understand ATX-LPA axis signaling in cancer and its potential as a therapeutic target. In this review, we discuss the evidence linking LPA signaling to cancer-related inflammation and its impact on cancer progression.

[1]  Duane D. Miller,et al.  Direct quantitative analysis of lysophosphatidic acid molecular species by stable isotope dilution electrospray ionization liquid chromatography-mass spectrometry. , 2001, Analytical biochemistry.

[2]  T. Wang,et al.  Inflammation, atrophy, and gastric cancer. , 2007, The Journal of clinical investigation.

[3]  He Zhu,et al.  Plasma levels of lysophosphatidic acid in ovarian cancer versus controls: a meta-analysis , 2015, Lipids in Health and Disease.

[4]  Y. Kishi,et al.  Autotaxin Is Overexpressed in Glioblastoma Multiforme and Contributes to Cell Motility of Glioblastoma by Converting Lysophosphatidylcholine TO Lysophosphatidic Acid* , 2006, Journal of Biological Chemistry.

[5]  Y. Kishi,et al.  Autotaxin Stabilizes Blood Vessels and Is Required for Embryonic Vasculature by Producing Lysophosphatidic Acid* , 2006, Journal of Biological Chemistry.

[6]  Eun Jin Seo,et al.  Autotaxin Regulates Maintenance of Ovarian Cancer Stem Cells through Lysophosphatidic Acid‐Mediated Autocrine Mechanism , 2016, Stem cells.

[7]  J. Chun,et al.  Lysophosphatidic acid receptors. , 2000, Molecular pharmacology.

[8]  Ganesh Venkatraman,et al.  Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes involved in drug resistance and oxidative stress responses: implications for cancer treatment , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  Toshio Mori,et al.  Possible involvement of lysophosphatidic acid receptor‐5 gene in the acquisition of growth advantage of rat tumor cells , 2011, Molecular carcinogenesis.

[10]  B. Giepmans,et al.  The ins and outs of lysophosphatidic acid signaling , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[11]  E. Goetzl,et al.  Characterization of a Novel Subtype of Human G Protein-coupled Receptor for Lysophosphatidic Acid* , 1998, The Journal of Biological Chemistry.

[12]  J. Salles,et al.  Production of lysophosphatidic acid in blister fluid: involvement of a lysophospholipase D activity. , 2005, The Journal of investigative dermatology.

[13]  T. Hla,et al.  Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors. , 2011, Chemical reviews.

[14]  P. Valet,et al.  Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid , 2011, Journal of Lipid Research.

[15]  D. Brindley,et al.  Lipid phosphate phosphatases and their roles in mammalian physiology and pathology , 2015, Journal of Lipid Research.

[16]  Peng Cheng,et al.  A mixed-crystal lanthanide zeolite-like metal-organic framework as a fluorescent indicator for lysophosphatidic acid, a cancer biomarker. , 2015, Journal of the American Chemical Society.

[17]  D. Hallahan,et al.  Autotaxin and LPA Receptors Represent Potential Molecular Targets for the Radiosensitization of Murine Glioma through Effects on Tumor Vasculature , 2011, PloS one.

[18]  Alberto Mantovani,et al.  Inflammation and cancer: back to Virchow? , 2001, The Lancet.

[19]  Eugene Y. Kim,et al.  Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. , 2013, Cancer cell.

[20]  Sarah Spiegel,et al.  International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature , 2010, Pharmacological Reviews.

[21]  T. Helleday,et al.  Lysophosphatidic acid receptor (LPAR) modulators: The current pharmacological toolbox. , 2015, Progress in lipid research.

[22]  D. Theodorescu,et al.  Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. , 2000, Molecular pharmacology.

[23]  J. Chun,et al.  Lysophospholipid receptors in drug discovery. , 2015, Experimental cell research.

[24]  J. Chun,et al.  Lysophospholipids and their receptors in the central nervous system. , 2013, Biochimica et biophysica acta.

[25]  D. Hallahan,et al.  Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines , 2013, Front. Oncol..

[26]  C. Wood,et al.  Autotaxin–Lysophosphatidic Acid Signaling Axis Mediates Tumorigenesis and Development of Acquired Resistance to Sunitinib in Renal Cell Carcinoma , 2013, Clinical Cancer Research.

[27]  Lei Wu,et al.  Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action. , 2009, World journal of gastroenterology.

[28]  F. Lin,et al.  Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy. , 2013, Biochimica et biophysica acta.

[29]  R. Lai,et al.  Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer. , 2015, Endocrine-related cancer.

[30]  Toshio Mori,et al.  Loss of lysophosphatidic acid receptor-3 enhances cell migration in rat lung tumor cells. , 2011, Biochemical and biophysical research communications.

[31]  M. Nöthen,et al.  G protein–coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth , 2008, Nature Genetics.

[32]  James I. Fells,et al.  Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. , 2009, Cancer research.

[33]  Y. Hoshida,et al.  The autotaxin-lysophosphatidic acid pathway emerges as a therapeutic target to prevent liver cancer , 2017, Molecular & cellular oncology.

[34]  Yun-Ju Lai,et al.  c-Src-Mediated Phosphorylation of TRIP6 Regulates Its Function in Lysophosphatidic Acid-Induced Cell Migration , 2005, Molecular and Cellular Biology.

[35]  Bernard P. Kok,et al.  Unlike two peas in a pod: lipid phosphate phosphatases and phosphatidate phosphatases. , 2012, Chemical reviews.

[36]  K. Harper,et al.  Autotaxin promotes cancer invasion via the lysophosphatidic acid receptor 4: participation of the cyclic AMP/EPAC/Rac1 signaling pathway in invadopodia formation. , 2010, Cancer research.

[37]  Alberto Mantovani,et al.  Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. , 2009, Carcinogenesis.

[38]  L. Daniel,et al.  Reactive oxygen species mediate lysophosphatidic acid induced signaling in ovarian cancer cells. , 2010, Free radical biology & medicine.

[39]  S. Georas,et al.  The Autotaxin–LPA Axis Emerges as a Novel Regulator of Lymphocyte Homing and Inflammation , 2014, The Journal of Immunology.

[40]  N. Samadi,et al.  Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. , 2011, Biochimie.

[41]  D. Brindley,et al.  Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate[S] , 2015, Journal of Lipid Research.

[42]  D. Budd,et al.  Development of Autotaxin Inhibitors: An Overview of the Patent and Primary Literature. , 2016, Journal of medicinal chemistry.

[43]  W. Moolenaar,et al.  Regulation and biological activities of the autotaxin-LPA axis. , 2009, Progress in lipid research.

[44]  David A. Egan,et al.  Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation , 2010, Proceedings of the National Academy of Sciences.

[45]  Yiling Lu,et al.  Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. , 2009, Cancer cell.

[46]  J. Chun,et al.  Age-Dependent Loss of Sperm Production in Mice via Impaired Lysophosphatidic Acid Signaling1 , 2008, Biology of reproduction.

[47]  M. Roizen,et al.  Hallmarks of Cancer: The Next Generation , 2012 .

[48]  Y. Rojanasakul,et al.  Inflammation and Lung Cancer: Roles of Reactive Oxygen/Nitrogen Species , 2008, Journal of toxicology and environmental health. Part B, Critical reviews.

[49]  Takao Shimizu,et al.  Current progress in non-Edg family LPA receptor research. , 2013, Biochimica et biophysica acta.

[50]  J. Gierse,et al.  A Novel Autotaxin Inhibitor Reduces Lysophosphatidic Acid Levels in Plasma and the Site of Inflammation , 2010, Journal of Pharmacology and Experimental Therapeutics.

[51]  F. Wuest,et al.  Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy , 2017, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  G. Ferry,et al.  Autotaxin Is Released from Adipocytes, Catalyzes Lysophosphatidic Acid Synthesis, and Activates Preadipocyte Proliferation , 2003, The Journal of Biological Chemistry.

[53]  A. Dubin,et al.  GPR92 as a New G12/13- and Gq-coupled Lysophosphatidic Acid Receptor That Increases cAMP, LPA5* , 2006, Journal of Biological Chemistry.

[54]  J. Chun,et al.  The absence of LPA receptor 2 reduces the tumorigenesis by ApcMin mutation in the intestine. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[55]  G. Prestwich,et al.  A Metabolically-Stabilized Phosphonate Analog of Lysophosphatidic Acid Attenuates Collagen-Induced Arthritis , 2013, PloS one.

[56]  P. Morin,et al.  PF‐8380 and Closely Related Analogs: Synthesis and Structure–Activity Relationship towards Autotaxin Inhibition and Glioma Cell Viability , 2013, Archiv der Pharmazie.

[57]  G. Mills,et al.  ATX-LPA receptor axis in inflammation and cancer , 2009, Cell cycle.

[58]  Y. Yung,et al.  Lysophosphatidic Acid Signaling in the Nervous System , 2015, Neuron.

[59]  Ruiwen Zhang,et al.  Anti-Inflammatory Agents for Cancer Therapy. , 2009, Molecular and cellular pharmacology.

[60]  G. Fuller,et al.  Analysis of the activation status of Akt, NFκB, and Stat3 in human diffuse gliomas , 2004, Laboratory Investigation.

[61]  Y. Yung,et al.  LPA receptor signaling: pharmacology, physiology, and pathophysiology , 2014, Journal of Lipid Research.

[62]  K. Miyazono,et al.  LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. , 2010, Blood.

[63]  J. Aoki,et al.  Two pathways for lysophosphatidic acid production. , 2008, Biochimica et biophysica acta.

[64]  P. Valet,et al.  Lysophosphatidic acid synthesis and release. , 2001, Prostaglandins & other lipid mediators.

[65]  P. Winter,et al.  Lysophosphatidic acid receptor LPAR6 supports the tumorigenicity of hepatocellular carcinoma. , 2015, Cancer research.

[66]  J. Garcia,et al.  Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells* , 2004, Journal of Biological Chemistry.

[67]  Y. Kishi,et al.  Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer , 2004, Laboratory Investigation.

[68]  G. Mills,et al.  Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production , 2002, The Journal of cell biology.

[69]  V. Natarajan,et al.  Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo. , 2009, The Biochemical journal.

[70]  J. Weiner,et al.  Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[71]  J. Chun,et al.  Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg2/Edg4) Lysophosphatidic Acid Receptor Knockout Mice: Signaling Deficits without Obvious Phenotypic Abnormality Attributable to lpa2 , 2002, Molecular and Cellular Biology.

[72]  L. Coussens,et al.  Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression , 2007, Breast Cancer Research.

[73]  Hiroyuki Arai,et al.  Molecular Cloning and Characterization of a Novel Human G-protein-coupled Receptor, EDG7, for Lysophosphatidic Acid* , 1999, The Journal of Biological Chemistry.

[74]  D C McMillan,et al.  Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer , 2006, British Journal of Cancer.

[75]  Wei Zhou,et al.  Lysophosphatidic Acid Stimulates Activation of Focal Adhesion Kinase and Paxillin and Promotes Cell Motility, via LPA1–3, in Human Pancreatic Cancer , 2013, Digestive Diseases and Sciences.

[76]  Jeannette Bigler,et al.  Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics , 2006, Nature Reviews Cancer.

[77]  D. Brindley,et al.  Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions , 2014, FEBS letters.

[78]  G. Giannelli,et al.  Tumor‐secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts , 2011, Hepatology.

[79]  Kyoko Noguchi,et al.  LPA receptors: subtypes and biological actions. , 2010, Annual review of pharmacology and toxicology.

[80]  A. Subramanian,et al.  Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition. , 2016, Cancer cell.

[81]  Yiling Lu,et al.  Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. , 2008, Journal of the National Cancer Institute.

[82]  Menggang Yu,et al.  Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma , 2010, Molecular Cancer.

[83]  S. Spiegel,et al.  Lysophospholipid receptor nomenclature review: IUPHAR Review 8 , 2014, British journal of pharmacology.

[84]  Y. Shiloh,et al.  Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks , 2010, Proceedings of the National Academy of Sciences.

[85]  J. Boeynaems,et al.  Cloning of a human heptahelical receptor closely related to the P2Y5 receptor. , 1997, Biochemical and biophysical research communications.

[86]  James I. Fells,et al.  Unique Ligand Selectivity of the GPR92/LPA5 Lysophosphatidate Receptor Indicates Role in Human Platelet Activation* , 2009, The Journal of Biological Chemistry.

[87]  K. Honoki,et al.  Lysophosphatidic acid signaling via LPA1 and LPA3 regulates cellular functions during tumor progression in pancreatic cancer cells , 2017, Experimental cell research.

[88]  D. Im,et al.  Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo , 2012, Cancer science.

[89]  C. Mummery,et al.  Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development , 2006, Molecular and Cellular Biology.

[90]  H. Ueda,et al.  Lysophosphatidic acid: chemical signature of neuropathic pain. , 2013, Biochimica et biophysica acta.

[91]  J. Mackey,et al.  Tumor‐induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[92]  G. Mills,et al.  The emerging role of lysophosphatidic acid in cancer , 2003, Nature Reviews Cancer.

[93]  A. Perrakis,et al.  Autotaxin: structure-function and signaling , 2014, Journal of Lipid Research.

[94]  O. Cummings,et al.  Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung. , 2007, Cancer research.

[95]  C. Madeddu,et al.  Inflammation and ovarian cancer. , 2012, Cytokine.

[96]  M. Hitt,et al.  Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[97]  Takao Shimizu,et al.  Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6* , 2009, The Journal of Biological Chemistry.

[98]  Y. Cong,et al.  Lysophosphatidic acid activates telomerase in ovarian cancer cells through hypoxia‐inducible factor‐1α and the PI3K pathway , 2008, Journal of cellular biochemistry.

[99]  G. Venkatraman,et al.  Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo , 2015, Journal of biomedical research.

[100]  Yutong Zhao,et al.  Regulation of Lysophosphatidic Acid-induced Epidermal Growth Factor Receptor Transactivation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells by Protein Kinase Cδ, Lyn Kinase, and Matrix Metalloproteinases* , 2006, Journal of Biological Chemistry.

[101]  G. Prestwich,et al.  Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three‐dimensional lung cancer xenograft model , 2010, Cancer.

[102]  K. Honoki,et al.  Lysophosphatidic acid (LPA) signaling via LPA4 and LPA6 negatively regulates cell motile activities of colon cancer cells. , 2017, Biochemical and biophysical research communications.

[103]  M. Tsao,et al.  Autotaxin expression in non-small-cell lung cancer. , 1999, American journal of respiratory cell and molecular biology.

[104]  Hiroshi Suzuki,et al.  LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing , 2005, Nature.

[105]  W. Moolenaar.  Development of Our Current Understanding of Bioactive Lysophospholipids , 2000, Annals of the New York Academy of Sciences.

[106]  D. Park,et al.  Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1α from human mesenchymal stem cells , 2010, Experimental & Molecular Medicine.

[107]  H. Arai,et al.  Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species , 2000, FEBS letters.

[108]  Lisa M. Coussens,et al.  Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression , 2007 .

[109]  J. Chun,et al.  Targeted Deletion of LPA5 Identifies Novel Roles for Lysophosphatidic Acid Signaling in Development of Neuropathic Pain* , 2012, The Journal of Biological Chemistry.

[110]  R. D'Hooge,et al.  LPA5 receptor plays a role in pain sensitivity, emotional exploration and reversal learning , 2012, Genes, brain, and behavior.

[111]  N. Sugimoto,et al.  The Edg family G protein-coupled receptors for lysophospholipids: their signaling properties and biological activities. , 2002, Journal of biochemistry.

[112]  Hua Yu,et al.  STATs in cancer inflammation and immunity: a leading role for STAT3 , 2009, Nature Reviews Cancer.

[113]  Takao Shimizu,et al.  Identification of p2y9/GPR23 as a Novel G Protein-coupled Receptor for Lysophosphatidic Acid, Structurally Distant from the Edg Family* , 2003, Journal of Biological Chemistry.

[114]  Kees Jalink,et al.  LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor , 2011, PloS one.

[115]  A. D. De Marzo,et al.  Prostate cancer and inflammation: the evidence , 2012, Histopathology.

[116]  J. Inazawa,et al.  Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). , 1995, Genomics.

[117]  H. Arai,et al.  Expression patterns of the lysophospholipid receptor genes during mouse early development , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[118]  Kazuhiro Nakamura,et al.  Both Plasma Lysophosphatidic Acid and Serum Autotaxin Levels are Increased in Chronic Hepatitis C , 2007, Journal of clinical gastroenterology.

[119]  N. Triballeau,et al.  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 Fib , 2017, Journal of medicinal chemistry.

[120]  M. Subler,et al.  Role of LPA4/p2y9/GPR23 in negative regulation of cell motility. , 2008, Molecular biology of the cell.

[121]  D. Tarin,et al.  Identification of genes associated with metastasis of mammary carcinoma in metastatic versus non-metastatic cell lines. , 2002, Anticancer research.

[122]  K. Fukuzawa,et al.  Identification of Human Plasma Lysophospholipase D, a Lysophosphatidic Acid-producing Enzyme, as Autotaxin, a Multifunctional Phosphodiesterase* , 2002, The Journal of Biological Chemistry.

[123]  J. Weiner,et al.  Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex , 1996, The Journal of cell biology.

[124]  S. Deivendran,et al.  The role of inflammation in cervical cancer. , 2014, Advances in experimental medicine and biology.

[125]  K. Honoki,et al.  Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells , 2014, Growth factors.

[126]  Yun-Ju Lai,et al.  PTPL1/FAP-1 Negatively Regulates TRIP6 Function in Lysophosphatidic Acid-induced Cell Migration* , 2007, Journal of Biological Chemistry.

[127]  M Markman,et al.  Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. , 1998, JAMA.

[128]  David I. Smith,et al.  Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[129]  M. López-Rodríguez,et al.  The status of the lysophosphatidic acid receptor type 1 (LPA1R) , 2015 .

[130]  Mandi M. Murph,et al.  Autotaxin – An Enzymatic Augmenter of Malignant Progression Linked to Inflammation , 2015 .

[131]  M. Bollen,et al.  Cancer Cell Expression of Autotaxin Controls Bone Metastasis Formation in Mouse through Lysophosphatidic Acid-Dependent Activation of Osteoclasts , 2010, PloS one.

[132]  B. Olde,et al.  Lysophosphatidic Acid Binds to and Activates GPR92, a G Protein-Coupled Receptor Highly Expressed in Gastrointestinal Lymphocytes , 2006, Journal of Pharmacology and Experimental Therapeutics.

[133]  M. Castellone,et al.  Thyroid cancer and inflammation , 2010, Molecular and Cellular Endocrinology.

[134]  A. Bengtsson,et al.  Gene expression profiling for the identification of G-protein coupled receptors in human platelets. , 2008, Thrombosis research.

[135]  G. Mills,et al.  Lysophosphatidic acid induction of urokinase plasminogen activator secretion requires activation of the p38MAPK pathway. , 2007, International journal of oncology.

[136]  J. Chun,et al.  The absence of LPA2 attenuates tumor formation in an experimental model of colitis-associated cancer. , 2009, Gastroenterology.

[137]  Gabor Tigyi,et al.  Lysophosphatidic Acid Inhibits CD8 T-cell Activation and Control of Tumor Progression , 2013, Cancer Immunology Research.

[138]  J. Chun,et al.  Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a retrovirus expression system. , 2000, Molecular pharmacology.

[139]  M. Suematsu,et al.  Constitutive Lymphocyte Transmigration across the Basal Lamina of High Endothelial Venules Is Regulated by the Autotaxin/Lysophosphatidic Acid Axis , 2013, The Journal of Immunology.

[140]  G. Halldén,et al.  P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[141]  D. Baker,et al.  Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine 1-Phosphate Generation in Blood* , 2002, The Journal of Biological Chemistry.