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https://www.readbyqxmd.com/read/29407582/nm23-downregulation-and-lysophosphatidic-acid-receptor-edg2-lpa1-upregulation-during-myeloid-differentiation-of-human-leukemia-cells
#1
Junko Okabe-Kado, Yuki Hagiwara-Watanabe, Nozomi Niitsu, Takashi Kasukabe, Yasuhiko Kaneko
The NM23 gene is overexpressed in many hematological malignancies and its overexpression predicts poor treatment outcomes. NM23 overexpression is thought to suppress myeloid differentiation of leukemia cells, but the molecular mechanism is unknown. In breast cancer cells, the lysophosphatidic acid (LPA) receptor EDG2/lpa1 was downregulated by NM23-H1 overexpression, and this reciprocal expression pattern was associated with suppressed or induced cell motility/metastasis. Here, we examined the relationship between EDG2 and NM23 expression during myeloid differentiation of leukemia cells...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29386184/lysophosphatidic-acid-induces-metabolic-reprogramming-in-ovarian-cancer-via-a-pseudohypoxic-response
#2
Ji Hee Ha, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Mingda Yan, Jeremy D Ward, Kar-Ming Fung, Katherine M Moxley, Anil K Sood, Ciro Isidoro, Priyabrata Mukherjee, Yong Sang Song, Danny N Dhanasekaran
Although hypoxia has been shown to reprogram cancer cells toward glycolytic shift, the identity of extrinsic stimuli that induce metabolic reprogramming independent of hypoxia, especially in ovarian cancer, is largely unknown. In this study, we use patient-derived ovarian cancer cells and high-grade serous ovarian cancer cell lines to demonstrate that lysophosphatidic acid (LPA), a lipid growth factor and GPCR ligand whose levels are substantially increased in ovarian cancer patients, triggers glycolytic shift in ovarian cancer cells...
January 31, 2018: Cancer Research
https://www.readbyqxmd.com/read/29378212/systemic-blockade-of-lpa1-3-lysophosphatidic-acid-receptors-by-ki16425-modulates-the-effects-of-ethanol-on-the-brain-and-behavior
#3
Laura Sánchez-Marín, David Ladrón de Guevara-Miranda, Mari Carmen Mañas-Padilla, Francisco Alén, Román D Moreno-Fernández, Caridad Díaz-Navarro, José Pérez-Del Palacio, María García-Fernández, Carmen Pedraza, Francisco J Pavón, Fernando Rodríguez de Fonseca, Luis J Santín, Antonia Serrano, Estela Castilla-Ortega
The systemic administration of lysophosphatidic acid (LPA) LPA1/3 receptor antagonists is a promising clinical tool for cancer, sclerosis and fibrosis-related diseases. Since LPA1 receptor-null mice engage in increased ethanol consumption, we evaluated the effects of systemic administration of an LPA1/3 receptor antagonist (intraperitoneal ki16425, 20 mg/kg) on ethanol-related behaviors as well as on brain and plasma correlates. Acute administration of ki16425 reduced motivation for ethanol but not for saccharine in ethanol self-administering Wistar rats...
January 26, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29369010/effects-of-lpa1-and-lpa6-on-the-regulation-of-colony-formation-activity-in-colon-cancer-cells-treated-with-anticancer-drugs
#4
Kaede Takahashi, Kaori Fukushima, Shiho Otagaki, Kaichi Ishimoto, Kanako Minami, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits a variety of cellular responses via the activation of G protein-coupled transmembrane LPA receptors (LPA receptor-1 (LPA1) to LPA6). The aim of our study was to investigate effects of LPA receptors on soft agar colony formation in colon cancer cells treated with anticancer drugs. DLD1 cells were treated with fluorouracil (5-FU) or cisplatin (CDDP) for at least six months (DLD-5FU and DLD-CDDP cells, respectively). LPAR1 gene expression was markedly elevated in DLD-5FU cells...
February 2018: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29337044/lysophosphatidic-acid-regulates-the-motility-of-mcf10ca1a-breast-cancer-cell-sheets-via-two-opposing-signaling-pathways
#5
Christina H Stuelten, Rachel M Lee, Wolfgang Losert, Carole A Parent
Aberrant cell migration leads to the dispersal of malignant cells. The ubiquitous lipid mediator lysophosphatidic acid (LPA) modulates cell migration and is implicated in tumor progression. Yet, the signaling cascades that regulate LPA's effect on cell motility remain unclear. Using time-lapse imaging and quantitative analyses, we studied the role of signaling cascades that act downstream of LPA on the motility of MCF10CA1a breast cancer cells. We found that LPA alters cell motility via two major signaling pathways...
January 11, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331665/blocking-lpa-dependent-signaling-increases-ovarian-cancer-cell-death-in-response-to-chemotherapy
#6
LeAnn C Rogers, Ryan R Davis, Naveen Said, Thomas Hollis, Larry W Daniel
The paradoxical role of reactive oxygen species in cell death versus cell survival establishes a delicate balance between chemotherapy efficacy and management of detrimental side effects. Normal proliferative signaling requires that cells remain inside a redox range that allows reversible protein oxidation to occur. Shifting the redox environment toward highly reducing or oxidizing states leads to cellular stress and cell death. Reactive oxygen species produced in response to Taxol and cisplatin treatment are necessary for effective cancer cell killing but the same ROS leads to damaging side effects in normal tissues...
January 4, 2018: Redox Biology
https://www.readbyqxmd.com/read/29329782/lpa-induced-migration-of-ovarian-cancer-cells-requires-activation-of-erm-proteins-via-lpa1-and-lpa2
#7
Jeongrak Park, Jin-Hyuck Jang, Seojin Oh, Minhye Kim, Changhoon Shin, Minseok Jeong, Kyun Heo, Jong Bae Park, Sang Ryong Kim, Yong-Seok Oh
Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian cancer. This phospholipid elicits a wide range of cancer cell responses, such as proliferation, trans-differentiation, migration, and invasion, via various G-protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling pathway via which LPA induces migration of ovarian cancer cells. LPA induced robust phosphorylation of ezrin/radixin/moesin (ERM) proteins, which are membrane-cytoskeleton linkers, in the ovarian cancer cell line OVCAR-3...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29328374/atx%C3%A2-lpa-axis-facilitates-estrogen%C3%A2-induced-endometrial-cancer-cell-proliferation-via-mapk-erk-signaling-pathway
#8
Guo Zhang, Yuan Cheng, Qi Zhang, Xiaoping Li, Jingwei Zhou, Jianliu Wang, Lihui Wei
Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX is a crucial factor that facilitates cancer progression; however, the effect of ATX on endometrial cancer has not been explored. The aim of the present study was to investigate the role of ATX in the progression of endometrial cancer. The immunohistochemical results revealed higher protein expression levels of ATX and LPA receptors (LPA 1, 2 and 3) in human endometrial cancer tissue than in non‑carcinoma tissue...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321663/lpa-signaling-is-regulated-through-the-primary-cilium-a-novel-target-in-glioblastoma
#9
Yuriy V Loskutov, Caryn L Griffin, Kristina M Marinak, Andrey Bobko, Naira V Margaryan, Werner J Geldenhuys, Jann N Sarkaria, Elena N Pugacheva
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29291160/a-dual-biomarker-detection-platform-for-quantitating-circulating-tumor-dna-ctdna
#10
Chunyan Cai, Zhenzhong Guo, Yiping Cao, Weiying Zhang, Yong Chen
Circulating tumor DNA (ctDNA), which includes DNA mutations, epigenetic alterations and other forms of tumor-specific abnormalities, is a promising "real-time" biomarker for noninvasive cancer assessment. Tumor DNA is of great value in the process of cancer treatment, including diagnostic and prognostic information before, during treatment and at progression. Here we introduce a peptide nucleic acids probe-gold nanoparticles (PNA-AuNPs) and lead phosphate apoferritin (LPA)-based dual biomarker detection platform, which could be used in a DNA biosensor to quantify ctDNA by detection of tumor-specific mutations and methylation of PIK3CA gene...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29258184/lysophospholipid-related-diseases-and-ppar%C3%AE-signaling-pathway
#11
REVIEW
Tamotsu Tsukahara, Yoshikazu Matsuda, Hisao Haniu
The nuclear receptor superfamily includes ligand-inducible transcription factors that play diverse roles in cell metabolism and are associated with pathologies such as cardiovascular diseases. Lysophosphatidic acid (LPA) belongs to a family of lipid mediators. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and an intracellular nuclear hormone receptor. In addition, several enzymes that utilize LPA as a substrate or generate it as a product are under its regulatory control...
December 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29198709/cholesterol-inhibits-entotic-cell-in-cell-formation-and-actomyosin-contraction
#12
Banzhan Ruan, Bo Zhang, Ang Chen, Long Yuan, Jianqing Liang, Manna Wang, Zhengrong Zhang, Jie Fan, Xiaochen Yu, Xin Zhang, Zubiao Niu, You Zheng, Songzhi Gu, Xiaoqing Liu, Hongli Du, Jufang Wang, Xianwen Hu, Lihua Gao, Zhaolie Chen, Hongyan Huang, Xiaoning Wang, Qiang Sun
Cell-in-cell structure is prevalent in human cancer, and associated with several specific pathophysiological phenomena. Although cell membrane adhesion molecules were found critical for cell-in-cell formation, the roles of other membrane components, such as lipids, remain to be explored. In this study, we attempted to investigate the effects of cholesterol and phospholipids on the formation of cell-in-cell structures by utilizing liposome as a vector. We found that Lipofectamine-2000, the reagent commonly used for routine transfection, could significantly reduce entotic cell-in-cell formation in a cell-specific manner, which is correlated with suppressed actomyosin contraction as indicated by reduced β-actin expression and myosin light chain phosphorylation...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29182028/altered-expression-of-lysophosphatidic-acid-receptors-in-association-with-the-synthesis-of-estrogens-and-androgens-in-type-1-endometrial-cancer-biology
#13
Tomasz Wasniewski, Izabela Woclawek-Potocka
To establish association between two main lysophosphatidic acid (LPA) receptors (LPAR2 and LPAR1) with the synthesis of estrogens and androgens in type-1 endometrial carcinoma (EC), we evaluated correlation of LPARs expression with expression of steroid 5 alpha-reductase 2 - aromatase (SRD5A2), or cytochrome P450 family 19 subfamily A member 1-5α-reductase (CYP19A1) in EC. Moreover, we aimed to investigate SRD5A2 and CYP19A1 expression in type 1 endometrial cancer and normal endometrium with its correlation to selected clinicopathological features...
November 28, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29178922/elevated-plasma-levels-of-lysophosphatidic-acid-and-aberrant-expression-of-lysophosphatidic-acid-receptors-in-adenomyosis
#14
Bicheng Yang, Liqun Wang, Xiaoju Wan, Yunjun Li, Xiaohong Yu, Yunna Qin, Yong Luo, Feng Wang, Ouping Huang
BACKGROUND: Given the important roles of the receptor-mediated lysophosphatidic acid (LPA) signaling in both reproductive tract function and gynecological cancers, it will be informative to investigate the potential role of LPA in the development of adenomyosis. The objective of this study was to evaluate the levels of LPA in plasma and the expression of six LPA receptors in the endometrial tissue collected from women with and without adenomyosis. METHODS: Plasma and endometrial tissue samples were collected form women with and without adenomyosis...
November 25, 2017: BMC Women's Health
https://www.readbyqxmd.com/read/29134466/glycogen-synthase-kinase-3%C3%AE-mediated-regulation-of-matrix-metalloproteinase-9-and-its-involvement-in-oral-squamous-cell-carcinoma-progression-and-invasion
#15
Kamdeo K Pramanik, Siddavaram Nagini, Abhay K Singh, Prajna Mishra, Tanushree Kashyap, Nidhi Nath, Manzar Alam, Ajay Rana, Rajakishore Mishra
PURPOSE: Oral squamous cell carcinoma (OSCC)-related deaths mainly result from invasion of the tumor cells into local cervical lymph nodes. It has been reported that progressive basement membrane loss promotes the metastatic and invasive capacities of OSCCs. Matrix metalloproteinase-9 (MMP-9) is known to play a central role in tumor progression and invasion. However, the role of MMP-9 in OSCC invasion has so far remained paradoxical and little is known about its regulation. Here, we aimed to assess MMP-9 expression regulation and its activation by glycogen synthase kinase-3β during human OSCC progression and invasion...
November 13, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29127342/chemical-analysis-of-morphological-changes-in-lysophosphatidic-acid-treated-ovarian-cancer-cells
#16
Karen A Bailey, Yuliya Klymenko, Peter E Feist, Amanda B Hummon, M Sharon Stack, Zachary D Schultz
Ovarian cancer (OvCa) cells are reported to undergo biochemical changes at the cell surface in response to treatment with lysophosphatidic acid (LPA). Here we use scanning electron microscopy (SEM) and multiplex coherent anti-Stokes Raman scattering (CARS) imaging via supercontinuum excitation to probe morphological changes that result from LPA treatment. SEM images show distinct shedding of microvilli-like features upon treatment with LPA. Analysis of multiplex CARS images can distinguish between molecular components, such as lipids and proteins...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120750/lysophosphatidate-signaling-the-tumor-microenvironment-s-new-nemesis
#17
Matthew G K Benesch, Zelei Yang, Xiaoyun Tang, Guanmin Meng, David N Brindley
Lysophosphatidate (LPA) is emerging as a potent mediator of cancer progression in the tumor microenvironment. Strategies for targeting LPA signaling have recently entered clinical trials for fibrosis. These therapies have potential to improve the efficacies of existing chemotherapies and radiotherapy by attenuating chronic inflammation, irrespective of diverse mutations within cancer cells.
November 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29046393/rac1-stimulated-macropinocytosis-enhances-g%C3%AE-%C3%AE-activation-of-pi3k%C3%AE
#18
Zahra Erami, Bassem D Khalil, Gilbert Salloum, Yanhua Yao, Jaclyn LoPiccolo, Aliaksei Shymanets, Bernd Nürnberg, Anne R Bresnick, Jonathan M Backer
Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex...
November 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29035165/development-of-highly-sensitive-cell-based-akt-kinase-elisa-for-monitoring-pi3k-beta-activity-and-compound-efficacy
#19
Mahesh Yanamandra, Labanyamoy Kole, Archana Giri, Sayan Mitra
Phosphatidylinositol-3 kinase (PI3K) pathway regulates multiple cellular functions involving cell survival, growth, motility proliferation, apoptosis, and adhesion. These are deregulated in various diseases such as cancer, atherosclerosis, and inflammation. PI3Ks phosphorylate phosphatidylinositol 4,5-biphosphate (PIP2) yielding phosphatidylinositol 3, 4, 5 triphosphate (PIP3) which in turn activate AKT kinase (serine/threonine kinase), the central enzyme in regulation of metabolic functions. Due to their implications in disease pathophysiology, PI3K/AKT inhibitors became attractive targets for pharmaceutical industries...
October 16, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29030599/genome-wide-meta-analysis-associates-hla-dqa1-drb1-and-lpa-and-lifestyle-factors-with-human-longevity
#20
Peter K Joshi, Nicola Pirastu, Katherine A Kentistou, Krista Fischer, Edith Hofer, Katharina E Schraut, David W Clark, Teresa Nutile, Catriona L K Barnes, Paul R H J Timmers, Xia Shen, Ilaria Gandin, Aaron F McDaid, Thomas Folkmann Hansen, Scott D Gordon, Franco Giulianini, Thibaud S Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M Bartz, Stella Trompet, Leslie A Lange, Laura Raffield, Ashley van der Spek, Tessel E Galesloot, Petroula Proitsi, Lisa R Yanek, Lawrence F Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D Børglum, Archie Campbell, Ellen W Demerath, Ilja Demuth, Jessica D Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M Hougaard, Mikko A Hurme, M Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E Medland, Lili Milani, Reka Nagy, William E R Ollier, Patricia A Peyser, Peter P Pramstaller, Paul M Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P Eline Slagboom, Blair H Smith, Jennifer A Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J A van Rooij, André L Verbeek, Sita H Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B Whitfield, Alan B Zonderman, Terho Lehtimäki, Michele K Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L R Kardia, Marina Ciullo, Diane M Becker, Andrew Wong, Bruce M Psaty, Cornelia M van Duijn, James G Wilson, J Wouter Jukema, Lambertus Kiemeney, André G Uitterlinden, Nora Franceschini, Kari E North, David R Weir, Andres Metspalu, Dorret I Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F Wilson
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated...
October 13, 2017: Nature Communications
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