@article{MTMT:35195205,
	title = {LPA suppresses HLA-DR expression in human melanoma cells: a potential immune escape mechanism involving LPAR1 and DR6-mediated release of IL-10},
	url = {https://m2.mtmt.hu/api/publication/35195205},
	author = {Major, Enikő and Lin, Kuan-Hung and Lee, Sue Chin and Káldi, Krisztina and Győrffy, Balázs and Tigyi, Gabor and Benyó, Zoltán},
	doi = {10.1038/s41401-024-01373-x},
	journal-iso = {ACTA PHARMACOL SIN},
	journal = {ACTA PHARMACOLOGICA SINICA},
	volume = {46},
	unique-id = {35195205},
	issn = {1671-4083},
	abstract = {While immune checkpoint inhibitors (ICIs) are promising in the treatment of metastatic melanoma, about half of patients do not respond well to them. Low levels of human leukocyte antigen-DR (HLA-DR) in tumors have been shown to negatively influence prognosis and response to ICIs. Lysophosphatidic acid (LPA) is produced in large amounts by melanoma and is abundantly present in the tumor microenvironment. LPA induces the release of various cytokines and chemokines from tumor cells, which affect cancer development, metastasis, and tumor immunity. In the present study, we investigated the role of LPA-induced IL-10 release in regulating HLA-DR expression and the underlying mechanisms in human melanoma cells. We showed that LPA (0.001–10 μM) dose-dependently increased DR6 transcript levels through activating LPAR1 in HEK293T cells. Knockdown of NF-κB1 abrogated the LPA-increased DR6 expression without affecting basal DR6 expression in both A2058 and A375 melanoma cell lines. LPA (10 µM) significantly increased IL-10 transcripts in A2058 and A375 melanoma cells, the effect was abolished by pharmacological inhibition of LPAR1 or knockdown of DR6. We found a statistically significant correlation between the expression of LPAR1, DR6 and IL-10 in human melanoma tissue and an association between increased expression of LPAR1 and reduced effectiveness of ICI therapy. We demonstrated that LPA (10 µM) markedly suppressed HLA-DR expression in both A375 and A2058 melanoma cells via activating the LPAR1-DR6-IL-10 pathway. These data suggest that the LPAR1-DR6-IL-10 autocrine loop could constitute a novel mechanism used by tumor cells to evade immunosurveillance by decreasing HLA-DR expression.},
	year = {2025},
	eissn = {1745-7254},
	pages = {222-230},
	orcid-numbers = {Major, Enikő/0000-0001-5854-9395; Káldi, Krisztina/0000-0002-5724-0182; Győrffy, Balázs/0000-0002-5772-3766; Tigyi, Gabor/0000-0001-5371-171X; Benyó, Zoltán/0000-0001-6015-0359}
}

@article{MTMT:35534771,
	title = {Deleting autotaxin in LysM+ myeloid cells impairs innate tumor immunity in models of metastatic melanoma},
	url = {https://m2.mtmt.hu/api/publication/35534771},
	author = {Dacheux, Mélanie A. and Norman, Derek D. and Shin, Yoojin and Tigyi, Gábor J. and Lee, Sue Chin},
	doi = {10.1016/j.isci.2024.110971},
	journal-iso = {ISCIENCE},
	journal = {ISCIENCE},
	volume = {27},
	unique-id = {35534771},
	year = {2024},
	eissn = {2589-0042},
	pages = {110971},
	orcid-numbers = {Lee, Sue Chin/0000-0002-7719-1648}
}

@article{MTMT:34904147,
	title = {Linking the Autotaxin-LPA Axis to Medicinal Cannabis and the Endocannabinoid System},
	url = {https://m2.mtmt.hu/api/publication/34904147},
	author = {Eymery, Mathias C. and Boumendjel, Ahcene and McCarthy, Andrew A. and Hausmann, Jens},
	doi = {10.3390/ijms25063212},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34904147},
	issn = {1661-6596},
	keywords = {CANNABINOIDS; endocannabinoid; Lysophosphatidic acid; tetrahydrocannabinol; AUTOTAXIN},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Boumendjel, Ahcene/0000-0002-1830-6409}
}

@article{MTMT:34942322,
	title = {Discovery of potent chromone-based autotaxin inhibitors inspired by cannabinoids},
	url = {https://m2.mtmt.hu/api/publication/34942322},
	author = {Eymery, Mathias Christophe and Nguyen, Kim-Anh and Basu, Shibom and Hausmann, Jens and Tran-Nguyen, Viet-Khoa and Seidel, Hans Peter and Gutierrez, Lola and Boumendjel, Ahcene and McCarthy, Andrew Aloysius},
	doi = {10.1016/j.ejmech.2023.115944},
	journal-iso = {EUR J MED CHEM},
	journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {263},
	unique-id = {34942322},
	issn = {0223-5234},
	keywords = {INHIBITORS; Indoles; molecular modelling; Chromones; cannabinoid; Structural biology; AUTOTAXIN; macromolecular X-ray crystallography},
	year = {2024},
	eissn = {1768-3254},
	orcid-numbers = {Basu, Shibom/0000-0001-6484-8236; Tran-Nguyen, Viet-Khoa/0000-0001-7497-333X; Boumendjel, Ahcene/0000-0002-1830-6409}
}

@article{MTMT:34954753,
	title = {BBT-877, a Novel Autotaxin Inhibitor, Abrogates Drug Resistance in Epithelial Ovarian Cancer Stem Cells},
	url = {https://m2.mtmt.hu/api/publication/34954753},
	author = {Kim, Jun se and Shin, Min joo and Lee, Seo yul and Choi, Seong min and Choi, Kyung-un and Suh, Dong-soo and Kim, Dae kyoung and Kim, Jae ho},
	doi = {10.21873/anticanres.16908},
	journal-iso = {ANTICANCER RES},
	journal = {ANTICANCER RESEARCH},
	volume = {44},
	unique-id = {34954753},
	issn = {0250-7005},
	keywords = {DRUG-RESISTANCE; AUTOTAXIN; epithelial ovarian cancer; Autotaxin inhibitor; cancer stem cell.},
	year = {2024},
	eissn = {1791-7530},
	pages = {1131-1142}
}

@article{MTMT:35306001,
	title = {Lysophosphatidic acid down-regulates human RIPK4 mRNA in keratinocyte- derived cell lines},
	url = {https://m2.mtmt.hu/api/publication/35306001},
	author = {Xu, Lei and Bajorski, Peter and Poligone, Brian},
	doi = {10.1371/journal.pone.0287444},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {19},
	unique-id = {35306001},
	year = {2024},
	eissn = {1932-6203}
}

@article{MTMT:34039147,
	title = {E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas},
	url = {https://m2.mtmt.hu/api/publication/34039147},
	author = {Lin, Kuan‐Hung and Lee, Sue Chin and Dacheux, Mélanie A. and Norman, Derek D. and Balogh, Andrea and Bavaria, Mitul and Lee, Hsinyu and Tigyi, Gabor},
	doi = {10.1096/fj.202300838R},
	journal-iso = {FASEB J},
	journal = {FASEB JOURNAL},
	volume = {37},
	unique-id = {34039147},
	issn = {0892-6638},
	year = {2023},
	eissn = {1530-6860},
	orcid-numbers = {Balogh, Andrea/0000-0002-3007-0793; Tigyi, Gabor/0000-0001-5371-171X}
}

@article{MTMT:34323969,
	title = {Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms},
	url = {https://m2.mtmt.hu/api/publication/34323969},
	author = {Toyohara, Tadashi and Yoshida, Michihiro and Miyabe, Katsuyuki and Hayashi, Kazuki and Naitoh, Itaru and Kondo, Hiromu and Hori, Yasuki and Kato, Akihisa and Kachi, Kenta and Asano, Go and Sahashi, Hidenori and Adachi, Akihisa and Kuno, Kayoko and Kito, Yusuke and Matsuo, Yoichi and Kataoka, Hiromi},
	doi = {10.1111/cas.15980},
	journal-iso = {CANCER SCI},
	journal = {CANCER SCIENCE: THE OFFICIAL JOURNAL OF THE JAPANESE CANCER ASSOCIATION},
	unique-id = {34323969},
	issn = {1347-9032},
	abstract = {Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX-LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX-LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target.Autotaxin (ATX), which is a secreted autocrine motility factor involved in the production of a lipid mediator, was highly expressed in pancreatic endocrine neoplasm (panNEN). The mRNA expression of mRNA in panNEN cell lines was higher than in pancreatic ductal adenocarcinoma cell lines. The serum level of ATX in panNEN patients was higher than in patients with other pancreatic diseases, and in immunohistochemical analysis of panNEN, tumor cells were stained strongly by ATX.image},
	keywords = {biomarker; neuroendocrine tumor; Lysophosphatidic acid; AUTOTAXIN; molecular target therapy},
	year = {2023},
	eissn = {1349-7006},
	orcid-numbers = {Toyohara, Tadashi/0009-0002-2302-0883; Yoshida, Michihiro/0000-0002-4167-2781}
}

@article{MTMT:34282674,
	title = {Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity},
	url = {https://m2.mtmt.hu/api/publication/34282674},
	author = {Turner, Jacqueline A. and Fredrickson, Malia A. and D'Antonio, Marc and Katsnelson, Elizabeth and MacBeth, Morgan and Van Gulick, Robert and Chimed, Tugs-Saikhan and McCarter, Martin and D'Alessandro, Angelo and Robinson, William A. and Couts, Kasey L. and Pelanda, Roberta and Klarquist, Jared and Tobin, Richard P. and Torres, Raul M.},
	doi = {10.1038/s41467-023-38933-4},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {14},
	unique-id = {34282674},
	issn = {2041-1723},
	abstract = {Lysophosphatidic acid is known to increase in concentration in multiple cancer types. Here, the authors show it affects CD8 T cell metabolism, phenotype, and effector functions, and plasma concentrations appear predictive of response to immunotherapy.Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression remain unknown. We show LPA receptor (LPAR) signaling by CD8 T cells promotes tolerogenic states via metabolic reprogramming and potentiating exhaustive-like differentiation to modulate anti-tumor immunity. We found LPA levels predict response to immunotherapy and Lpar5 signaling promotes cellular states associated with exhausted phenotypes on CD8 T cells. Importantly, we show that Lpar5 regulates CD8 T cell respiration, proton leak, and reactive oxygen species. Together, our findings reveal that LPA serves as a lipid-regulated immune checkpoint by modulating metabolic efficiency through LPAR5 signaling on CD8 T cells. Our study offers key insights into the mechanisms governing adaptive anti-tumor immunity and demonstrates LPA could be exploited as a T cell directed therapy to improve dysfunctional anti-tumor immunity.},
	year = {2023},
	eissn = {2041-1723},
	orcid-numbers = {Turner, Jacqueline A./0000-0002-6638-1956; MacBeth, Morgan/0000-0003-1299-0999; D'Alessandro, Angelo/0000-0002-2258-6490}
}

@article{MTMT:33934159,
	title = {Can precancerous stem cells be risk markers for malignant transformation in the oral mucosa ?},
	url = {https://m2.mtmt.hu/api/publication/33934159},
	author = {Wang, Shan and Ying, Liu and Yu, Shu-Yi and Bai, Jie and Hao, Chunbo},
	doi = {10.1186/s11658-023-00441-0},
	journal-iso = {CELL MOL BIOL LETT},
	journal = {CELLULAR AND MOLECULAR BIOLOGY LETTERS},
	volume = {28},
	unique-id = {33934159},
	issn = {1425-8153},
	abstract = {Accurate assessment of the carcinogenic potential of oral mucosal diseases can significantly reduce the prevalence of oral cancer. We speculate that precancerous stem cells (pCSCs) arise during the evolution of carcinomas based on long-term experimental findings, published literature, and the cancer stem cell (CSC) theory, wherein pCSCs exist in precancerous lesions and have characteristics of both CSCs and normal stem cells. This apparently contradictory feature may be the foundation of the reversible transformation of precancerous lesions. Predicting malignant transformation in potentially malignant oral illnesses would allow for focused treatment, prognosis, and secondary prevention. Currently available clinical assays for chromosomal instability and DNA aneuploidy have several deficiencies. We hope that our study will increase attention to pCSC research and lead to the development of novel strategies for the prevention and treatment of oral cancer by identifying pCSC markers.},
	keywords = {malignant transformation; dysplasia; Oral cancer; Cancer stem cells; Precancerous stem cells},
	year = {2023},
	eissn = {1689-1392}
}

@article{MTMT:33410131,
	title = {Long-term prediction of hepatocellular carcinoma using serum autotaxin levels after antiviral therapy for hepatitis C},
	url = {https://m2.mtmt.hu/api/publication/33410131},
	author = {Ando, Wataru and Kaneko, Fumihiko and Shimamoto, Satoshi and Igarashi, Koji and Otori, Katsuya and Yokomori, Hiroaki},
	doi = {10.1016/j.aohep.2022.100660},
	journal-iso = {ANN HEPATOL},
	journal = {ANNALS OF HEPATOLOGY - OFFICIAL JOURNAL OF THE MEXICAN ASSOCIATION OF HEPATOLOGY},
	volume = {27},
	unique-id = {33410131},
	issn = {1665-2681},
	abstract = {Introduction and objectives: Continuous monitoring for hepatocellular carcinoma is necessary following treatment with direct-acting antivirals in patients with hepatitis C virus infection. We investigated whether the long-term follow-up of serum autotaxin levels could predict the development of hepatocellular carcinoma. Patients and Methods: This prospective observational study enrolled adult patients with chronic hepatitis C virus infection who presented to the study center from January 2016 to March 2021. Among the patients who achieved a sustained viral response, the relationship between the development of hepatocellular carcinoma and serum autotaxin levels was assessed before treatment with direct-acting antivirals; at the end of therapy; at 12 and 24 weeks; and at 12, 24, 36, and 48 months after treatment.Results: Data were analyzed for 139 patients. Thirteen patients developed hepatocellular carcinoma 48 months after treatment. The cut-off serum autotaxin values that predicted hepatocellular carcinoma after 24 weeks were 1.22 (men) and 1.92 (women) mg/L. The area under the curve for serum autotaxin was 0.83 (95% confidence interval [CI]:0.71-0.95) in men and 0.90 (95% CI: 0.82-0.99) in women. The positive predictive value of serum autotaxin was 0.208 (95% CI: 0.139-0.248), and the negative predictive value was 0.971 (95% CI: 0.939-0.990). The cumulative incidence of hepatocellular carcinoma was significantly higher when serum autotaxin levels were above the cut-off value after 24 weeks (p < 0.0001).Conclusions: Serum autotaxin is a candidate biomarker for predicting hepatocellular carcinoma during the long-term follow-up of patients with a sustained viral response following treatment with direct-acting antivirals. (c) 2022 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)},
	keywords = {Hepatocellular carcinoma; AUTOTAXIN; DIRECT-ACTING ANTIVIRALS; WFA plus; -M2BP},
	year = {2022},
	eissn = {1665-2681},
	orcid-numbers = {Ando, Wataru/0000-0001-7085-1458; Igarashi, Koji/0000-0002-5007-7079}
}

@article{MTMT:33138340,
	title = {Designing Dual Inhibitors of Autotaxin-LPAR GPCR Axis},
	url = {https://m2.mtmt.hu/api/publication/33138340},
	author = {Banerjee, Souvik and Lee, Suechin and Norman, Derek D. and Tigyi, Gabor},
	doi = {10.3390/molecules27175487},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {27},
	unique-id = {33138340},
	issn = {1431-5157},
	abstract = {The ATX-LPA-LPAR1 signaling pathway plays a universal role in stimulating diverse cellular responses, including cell proliferation, migration, survival, and invasion in almost every cell type. The ATX-LPAR1 axis is linked to several metabolic and inflammatory diseases including cancer, fibrosis, and rheumatoid arthritis. Numerous selective ATX or LPAR1 inhibitors have been developed and so far, their clinical efficacy has only been evaluated in idiopathic pulmonary fibrosis. None of the ATX and LPAR1 inhibitors have advanced to clinical trials for cancer and rheumatoid arthritis. Nonetheless, several research groups, including ours, have shown considerable benefit of simultaneous ATX and LPAR1 inhibition through combination therapy. Recent research suggests that dual-targeting therapies are superior to combination therapies that use two selective inhibitors. However, limited reports are available on ATX-LPAR1 dual inhibitors, potentially due to co-expression of multiple different LPARs with close structural similarities at the same target. In this review, we discuss rational design and future directions of dual ATX-LPAR1 inhibitors.},
	year = {2022},
	eissn = {1420-3049},
	orcid-numbers = {Banerjee, Souvik/0000-0002-7811-2577; Lee, Suechin/0000-0002-7719-1648; Norman, Derek D./0000-0002-5626-6399; Tigyi, Gabor/0000-0001-5371-171X}
}

@article{MTMT:32377829,
	title = {Identification of Metabolic-Associated Genes for the Prediction of Colon and Rectal Adenocarcinoma},
	url = {https://m2.mtmt.hu/api/publication/32377829},
	author = {Cui, Yanfen and Han, Baoai and Zhang, He and Liu, Hui and Zhang, Fei and Niu, Ruifang},
	doi = {10.2147/OTT.S297134},
	journal-iso = {ONCOTARGETS THER},
	journal = {ONCOTARGETS AND THERAPY},
	volume = {14},
	unique-id = {32377829},
	issn = {1178-6930},
	abstract = {Background and Aim: Uncontrolled proliferation is the most prominent biological feature of tumors. In order to rapidly proliferate, tumor cells regulate their metabolic behavior by controlling the expression of metabolism-related genes (MRGs) to maximize the utilization of available nutrients. In this study, we aimed to construct prognosis models for colorectal adenocarcinoma (COAD) and rectum adenocarcinoma (READ) using MRGs to predict the prognoses of patients.Methods: We first acquired the gene expression profiles of COAD and READ from the TCGA database, and then utilized univariate Cox analysis, Lasso regression, and multivariable Cox analysis to identify the MRGs for risk models.Results: Eight genes (CPT1C, PLCB2, PLA2G2D, GAUL ENPP2, PIP4K2B, GPX3, and GSR) in the colon cancer risk model and six genes (TDO2, PKLR, GAUL EARS2, ACO1, and WAS) in the rectal cancer risk model were identified successfully. Multivariate Cox analysis indicated that these two models could accurately and independently predict overall survival (OS) for patients with COAD or READ. Furthermore, functional enrichment analysis was used to identify the metabolism pathway of MRGs in the risk models and analyzed these genes comprehensively. Then, we verified the prognosis model in independent COAD cohorts (GSE17538) and detected the correlations of the protein expression levels of GSR and ENPP2 with prognosis for COAD or READ.Conclusion: In this study, 14 MRGs were identified as potential prognostic biomarkers and therapeutic targets for colorectal cancer.},
	keywords = {Prognosis; colon adenocarcinoma; GSR; ENPP2; metabolism-related gene; rectum adenocarcinoma},
	year = {2021},
	eissn = {1178-6930},
	pages = {2259-2277},
	orcid-numbers = {Zhang, Fei/0000-0001-7434-7339}
}

@article{MTMT:32341809,
	title = {Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling},
	url = {https://m2.mtmt.hu/api/publication/32341809},
	author = {Jiang, Yinan and Guo, Yichen and Hao, Jinjin and Guenter, Rachael and Lathia, Justin and Beck, Adam W. and Hattaway, Reagan and Hurst, Douglas and Wang, Qiming Jane and Liu, Yehe and Cao, Qi and Krontiras, Helen and Chen, Herbert and Silverstein, Roy and Ren, Bin},
	doi = {10.1038/s42003-021-02308-6},
	journal-iso = {COMMUN BIOL},
	journal = {COMMUNICATIONS BIOLOGY},
	volume = {4},
	unique-id = {32341809},
	abstract = {Jiang, Guo, Hao et al. investigate the role of the tumour microenvironment in breast cancer stem cell regulation and identify an arteriolar niche in which BCSCs tended to be enriched in human estrogen receptor positive breast cancer. Here, BCSCs are found to interact with arteriolar endothelial cells through LPA/PKD-1 signalling-mediated arteriolar differentiation of ECs and self-renewal of BCSCs.Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues. Intriguingly, BCSCs tend to be enriched within the arteriolar niche in human estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of ECs and self-renewal of CSCs likely via differential regulation of CD36 transcription. This study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs.},
	year = {2021},
	eissn = {2399-3642}
}

@article{MTMT:32377828,
	title = {Autotaxin-LPA Axis in Obesity and Obesity-related Diseases},
	url = {https://m2.mtmt.hu/api/publication/32377828},
	author = {Yin Nan and Zhang Jun-Jie},
	doi = {10.16476/j.pibb.2020.0345},
	journal-iso = {PROG BIOCHEM BIOPHYS},
	journal = {PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS},
	volume = {48},
	unique-id = {32377828},
	issn = {1000-3282},
	abstract = {Lysophosphatidic acid (LPA), a set of bioactive lipid species with simple structure, is able to regulate various cellular activities, and participates in a variety of physiological and pathological processes via binding to the LPA receptors, a series of G protein coupled receptors on cellular membrane. Autotaxin (ATX) is a secretory glycoprotein with lysophosphatidase D (lysoPLD) activity to generate LPA from lysophosphatidylcholine (LPC), which is the main source of circulating LPA. Recently, increasing evidences have revealed that ATX is highly expressed in mature adipocytes and that the ATX-LPA axis plays a role in obesity and obesity -related disorder of glucose and lipid metabolism. The ATX-LPA axis has been regarded as the novel therapeutic target for obesity related diseases. In the present paper, we will review the research progresses of ATX-LPA axis in obesity and obesity -related diseases, such as insulin resistance and nonalcoholic fatty liver disease.},
	keywords = {OBESITY; Insulin Resistance; adipocyte; Lysophosphatidic acid; AUTOTAXIN; Nonalcoholic fatty liver disease},
	year = {2021},
	eissn = {1000-3282},
	pages = {768-778}
}

@article{MTMT:31688885,
	title = {Molecular modelling guided design, synthesis and QSAR analysis of new small molecule non-lipid autotaxin inhibitors},
	url = {https://m2.mtmt.hu/api/publication/31688885},
	author = {Banerjee, Souvik and Norman, Derek D. and Deng, Shanshan and Fakayode, Sayo O. and Lee, Sue Chin and Parrill, Abby L. and Li, Wei and Miller, Duane D. and Tigyi, Gabor J.},
	doi = {10.1016/j.bioorg.2020.104188},
	journal-iso = {BIOORG CHEM},
	journal = {BIOORGANIC CHEMISTRY},
	volume = {103},
	unique-id = {31688885},
	issn = {0045-2068},
	abstract = {The lysophospholipase D autotaxin (ATX) generates lysophosphatidic acid (LPA) that activates six cognate G-protein coupled receptors (GPCR) in cancerous cells, promoting their motility and invasion. Four novel compounds were generated aided by molecular docking guided design and synthesis techniques to obtain new dual inhibitors of ATX and the lysophosphatidic acid receptor subtype 1 (LPAR1). Biological evaluation of these compounds revealed two compounds, 10 and 11, as new ATX enzyme inhibitors with potencies in the range of 218-220 nM and water solubility ( > 100 mu g/mL), but with no LPAR1 inhibitory activity. A QSAR model was generated that included four newly designed compounds and twenty-one additional compounds that we have reported previously. The QSAR model provided excellent predictability of the pharmacological activity and potency among structurally related drug candidates. This model will be highly useful in guiding the synthesis of new ATX inhibitors in the future.},
	keywords = {QSAR; sulfonamide; PCA; Molecular docking; morpholine; ATX; tetrahydropyran; LPAR1 inhibitor},
	year = {2020},
	eissn = {1090-2120}
}

@article{MTMT:31249911,
	title = {Autotaxin and breast cancer: Towards overcoming treatment barriers and sequelae},
	url = {https://m2.mtmt.hu/api/publication/31249911},
	author = {Benesch, M.G.K. and Tang, X. and Brindley, D.N.},
	doi = {10.3390/cancers12020374},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {12},
	unique-id = {31249911},
	year = {2020},
	eissn = {2072-6694}
}

@article{MTMT:31692726,
	title = {Autotaxin: An Early Warning Biomarker for Acute-on-chronic Liver Failure},
	url = {https://m2.mtmt.hu/api/publication/31692726},
	author = {Nie, Caiyun and Zhang, Lei and Chen, Xiaobing and Li, Ying and Ha, Fushuang and Liu, Hua and Han, Tao},
	doi = {10.14218/JCTH.2020.00045},
	journal-iso = {J CLIN TRANSL HEPATO},
	journal = {JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY},
	volume = {8},
	unique-id = {31692726},
	issn = {2310-8819},
	abstract = {Background and Aims: Recent accumulating evidence indicates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF. Methods: Serum ATX was measured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrhosis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay. Results: SerumATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Serum ATX >= 584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95% confidence interval of 1.106-20.392, p=0.036). Conclusions: Serum ATX level may be a useful early warning biomarker for ACLF.},
	keywords = {SERUM; biomarker; liver failure; Autotaxin (ATX)},
	year = {2020},
	eissn = {2225-0719},
	pages = {240-245}
}

@article{MTMT:31395918,
	title = {Adipocytes in Breast Cancer, the Thick and the Thin},
	url = {https://m2.mtmt.hu/api/publication/31395918},
	author = {Rybinska, Ilona and Agresti, Roberto and Trapani, Anna and Tagliabue, Elda and Triulzi, Tiziana},
	doi = {10.3390/cells9030560},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {9},
	unique-id = {31395918},
	abstract = {It is well established that breast cancer development and progression depend not only on tumor-cell intrinsic factors but also on its microenvironment and on the host characteristics. There is growing evidence that adipocytes play a role in breast cancer progression. This is supported by: (i) epidemiological studies reporting the association of obesity with a higher cancer risk and poor prognosis, (ii) recent studies demonstrating the existence of a cross-talk between breast cancer cells and adipocytes locally in the breast that leads to acquisition of an aggressive tumor phenotype, and (iii) evidence showing that cancer cachexia applies also to fat tissue and shares similarities with stromal-carcinoma metabolic synergy. This review summarizes the current knowledge on the epidemiological link between obesity and breast cancer and outlines the results of the tumor-adipocyte crosstalk. We also focus on systemic changes in body fat in patients with cachexia developed in the course of cancer. Moreover, we discuss and compare adipocyte alterations in the three pathological conditions and the mechanisms through which breast cancer progression is induced.},
	keywords = {C-REACTIVE PROTEIN; ADIPOCYTES; TUMOR-NECROSIS-FACTOR; OBESITY; breast cancer; BODY-MASS INDEX; Adipokines; MESENCHYMAL TRANSITION; leptin receptor; ESTROGEN-RECEPTOR-ALPHA; SUBCUTANEOUS ADIPOSE-TISSUE; cancer associated adipocytes (CAAs); CROWN-LIKE STRUCTURES; LINKS OBESITY},
	year = {2020},
	eissn = {2073-4409},
	orcid-numbers = {Rybinska, Ilona/0000-0003-4871-9922; Tagliabue, Elda/0000-0001-9877-2903; Triulzi, Tiziana/0000-0003-3050-8676}
}

@article{MTMT:31692725,
	title = {The FOXM1/ATX signaling contributes to pancreatic cancer development},
	url = {https://m2.mtmt.hu/api/publication/31692725},
	author = {Xie, Dacheng and Yu, Shijun and Li, Li and Quan, Ming and Gao, Yong},
	journal-iso = {AM J TRANSL RES},
	journal = {AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH},
	volume = {12},
	unique-id = {31692725},
	issn = {1943-8141},
	abstract = {Both autotaxin (ATX) and Forkhead Box M1 (FOXM1) have been commonly recognized as oncogenes in multiple types of human malignancies. However, the expression and biological functions of ATX in pancreatic ductal adenocarcinoma (PDAC), and its correlation with FOXM1 are poorly understood. The present study aimed to investigate their correlation and biological consequences in PDAC development. By dual luciferase reporter and chromatin immunoprecipitation assays, we found that ATX was a downstream transcriptional target gene of FOXM1. Further cellular functional experiments indicated that ATX was required for FOXM1-mediated PDAC cell proliferation and migration. Data from molecular biological experiments showed that ATX could enhance FOXM1 expression in turn by inhibiting the Hippo signaling pathway, suggesting that ATX and FOXM1 formed a positive feedback loop to facilitate PDAC progression. Using immunohistochemistry (IHC) method, both ATX and FOXM1 expression were found to be frequently up-regulated in PDAC tumor tissues when compared with adjacent normal tissues, and elevated ATX and FOXM1 expression were positively correlated with each other. In conclusion, the present work identified a positive feedback loop between ATX and FOXM1 which promotes PDAC cell proliferation and migration.},
	keywords = {PROLIFERATION; MIGRATION; Pancreatic cancer; ATX; Foxm1},
	year = {2020},
	eissn = {1943-8141},
	pages = {4478-4487}
}

@article{MTMT:30909170,
	title = {An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases},
	url = {https://m2.mtmt.hu/api/publication/30909170},
	author = {Law, Shi-Hui and Chan, Mei-Lin and Marathe, Gopal K. and Parveen, Farzana and Chen, Chu-Huang and Ke, Liang-Yin},
	doi = {10.3390/ijms20051149},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {20},
	unique-id = {30909170},
	issn = {1661-6596},
	abstract = {Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A(2) (PLA(2)). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA(2) increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A(1) activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.},
	keywords = {LYSOPHOSPHATIDYLCHOLINE; AUTOTAXIN; lipoprotein-associated phospholipase A(2); lysophosphatidylcholine acyltransferase; lysophospholipase A(1); G protein-coupled receptor G2A},
	year = {2019},
	eissn = {1422-0067},
	orcid-numbers = {Ke, Liang-Yin/0000-0002-2547-0987}
}

@article{MTMT:30909209,
	title = {LPA(1), LPA(2), LPA(4), and LPA(6) receptor expression during mouse brain development},
	url = {https://m2.mtmt.hu/api/publication/30909209},
	author = {Suckau, Olga and Gross, Isabel and Schroetter, Sandra and Yang, Fan and Luo, Jiankai and Wree, Andreas and Chun, Jerold and Baska, David and Baumgart, Jan and Kano, Kuniyuki and Aoki, Junken and Braeuer, Anja U.},
	doi = {10.1002/dvdy.23},
	journal-iso = {DEV DYNAM},
	journal = {DEVELOPMENTAL DYNAMICS},
	volume = {248},
	unique-id = {30909209},
	issn = {1058-8388},
	abstract = {Background LPA is a small bioactive phospholipid that acts as an extracellular signaling molecule and is involved in cellular processes, including cell proliferation, migration, and differentiation. LPA acts by binding and activating at least six known G protein-coupled receptors: LPA(1-6). In recent years, LPA has been suggested to play an important role both in normal neuronal development and under pathological conditions in the nervous system. Results We show the expression pattern of LPA receptors during mouse brain development by using qRT-PCR, in situ hybridization, and immunocytochemistry. Only LPA(1), LPA(2,) LPA(4,) and LPA(6) mRNA transcripts were detected throughout development stages from embryonic day 16 until postnatal day 30 of hippocampus, neocortex, cerebellum, and bulbus olfactorius in our experiments, while expression of LPA(3) and LPA(5) genes was below detection level. In addition to our qRT-PCR results, we also analyzed the cellular protein expression of endogenous LPA receptors, with focus on LPA(1) and LPA(2) within postnatal brain slices and primary neuron differentiation with and without cytoskeleton stabilization and destabilization. Conclusions The expression of LPA receptors changes depends on the developmental stage in mouse brain and in cultured hippocampal primary neurons. Interestingly, we found that commercially available antibodies for LPA receptors are largely unspecific.},
	keywords = {Microtubule; Lysophosphatidic acid; Growth cone; qRT-PCR; G protein-coupling receptor; primary brain cells},
	year = {2019},
	eissn = {1097-0177},
	pages = {375-395}
}

@article{MTMT:30610562,
	title = {Regulation of tumor cell – Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis},
	url = {https://m2.mtmt.hu/api/publication/30610562},
	author = {Tigyi, Gabor and Yue, Junming and Norman, Derek D. and Szabó, Erzsébet and Balogh, Andrea and Balazs, Louisa and Zhao, Guannan and Lee, Sue Chin},
	doi = {10.1016/j.jbior.2018.09.008},
	journal-iso = {ADV BIOL REGUL},
	journal = {ADVANCES IN BIOLOGICAL REGULATION},
	volume = {71},
	unique-id = {30610562},
	issn = {2212-4926},
	year = {2019},
	eissn = {2212-4934},
	pages = {183-193},
	orcid-numbers = {Tigyi, Gabor/0000-0001-5371-171X; Balogh, Andrea/0000-0002-3007-0793}
}

@article{MTMT:31243008,
	title = {Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside},
	url = {https://m2.mtmt.hu/api/publication/31243008},
	author = {Xu, Yan},
	doi = {10.3390/cancers11101523},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {11},
	unique-id = {31243008},
	abstract = {Since the clear demonstration of lysophosphatidic acid (LPA)'s pathological roles in cancer in the mid-1990s, more than 1000 papers relating LPA to various types of cancer were published. Through these studies, LPA was established as a target for cancer. Although LPA-related inhibitors entered clinical trials for fibrosis, the concept of targeting LPA is yet to be moved to clinical cancer treatment. The major challenges that we are facing in moving LPA application from bench to bedside include the intrinsic and complicated metabolic, functional, and signaling properties of LPA, as well as technical issues, which are discussed in this review. Potential strategies and perspectives to improve the translational progress are suggested. Despite these challenges, we are optimistic that LPA blockage, particularly in combination with other agents, is on the horizon to be incorporated into clinical applications.},
	keywords = {lysophosphatidic acid (LPA); cancer stem cell (CSC); Autotaxin (ATX); ovarian cancer (OC); electrospray ionization tandem mass spectrometry (ESI-MS/MS); G-protein coupled receptor (GPCR); lipid phosphate phosphatase enzymes (LPPs); phospholipase A(2) enzymes (PLA(2)s); nuclear receptor peroxisome proliferator-activated receptor (PPAR); sphingosine-1 phosphate (S1P)},
	year = {2019},
	eissn = {2072-6694}
}

@article{MTMT:31243009,
	title = {Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms},
	url = {https://m2.mtmt.hu/api/publication/31243009},
	author = {Yang, Linfei and Yu, Xiao and Yang, Yongchao},
	doi = {10.1530/EC-18-0356},
	journal-iso = {ENDOCR CONNECT},
	journal = {ENDOCRINE CONNECTIONS},
	volume = {7},
	unique-id = {31243009},
	issn = {2049-3614},
	abstract = {Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-nodemetastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation.},
	keywords = {INVASION; ATX; signal transducer and activator of transcription 3; Pancreatic neuroendocrine neoplasms; pNEN},
	year = {2018},
	eissn = {2049-3614},
	pages = {1299-1307}
}