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LPA Cancer

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https://www.readbyqxmd.com/read/29198709/cholesterol-inhibits-entotic-cell-in-cell-formation-and-actomyosin-contraction
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28971574/aberrant-lipid-metabolism-in-cancer-cells-the-role-of-oncolipid-activated-signaling
#10
REVIEW
Upasana Ray, Sib Sankar Roy
Metabolic activity of malignant cells is very different from that of their nontransformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. In particular, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this for therapeutic benefit. Alterations in lipid metabolism are one of the main aspects of metabolic rewiring of transformed cells...
October 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28939644/role-of-lysophosphatidic-acid-and-its-receptors-in-the-kidney
#11
Frank Park, Duane Miller
Lysophosphatidic acid (LPA) is a bioactive phospholipid, which can exert diverse biological effects in various diseased states of the kidney by activating at least 6 cognate G-protein coupled receptors and its complex network of heterotrimeric G-proteins. In many models of acute and chronic kidney injury, pathological elevations in LPA promotes abnormal changes in renal tubular epithelial cell architecture by activating apoptotic signaling, recruit immune cells to the site of injury, and stimulate pro-fibrotic signaling by increasing gene transcription...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28938552/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#12
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910191/lysophosphatidic-acid-is-a-biomarker-for-peritoneal-carcinomatosis-of-gastric-cancer-and-correlates-with-poor-prognosis
#13
Ruolan Zeng, Bin Li, Junhui Huang, Meizuo Zhong, Li Li, Chaojun Duan, Shan Zeng, Jin Huang, Wei Liu, Jingchen Lu, Youhong Tang, Lingming Zhou, Yiping Liu, Jianhuang Li, Zhengxi He, Quan Wang, Youyi Dai
BACKGROUND: Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. Thus, it is important to identify an ideal biomarker for PC. METHODS: Plasma and ascites samples were collected from gastric cancer patients with PC and a control group. Lysophosphatidic acid (LPA) levels were tested and analyzed. RESULTS: The plasma LPA levels of gastric cancer patients with PC were significantly higher than those in gastric cancer patients after radical resection (p = 0...
September 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28865867/a-longitudinal-study-of-promis-pediatric-symptom-clusters-in-children-undergoing-chemotherapy
#14
Jichuan Wang, Shana Jacobs, Darren A Dewalt, Emily Stern, Heather Gross, Pamela S Hinds
CONTEXT: Children in treatment for cancer experience multiple, troubling and interrelated symptoms. Analyzing the interrelatedness of symptoms and how that changes during treatment could yield clinically relevant patient profiles to guide patient care. OBJECTIVES: The aims were to identify a) pediatric profiles with respect to PROMIS symptom measures, b) changes in profile status throughout a chemotherapy cycle, and c) if a baseline single-item fatigue measure could significantly predict symptom profile status and its changes...
August 30, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28854359/lysophosphatidic-acid-receptor-4-activation-augments-drug-delivery-in-tumors-by-tightening-endothelial-cell-cell-contact
#15
Kazuhiro Takara, Daisuke Eino, Koji Ando, Daisuke Yasuda, Hisamichi Naito, Yohei Tsukada, Tomohiro Iba, Taku Wakabayashi, Fumitaka Muramatsu, Hiroyasu Kidoya, Shigetomo Fukuhara, Naoki Mochizuki, Satoshi Ishii, Haruhiko Kishima, Nobuyuki Takakura
Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6)...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28792932/structural-insights-into-ligand-recognition-by-the-lysophosphatidic-acid-receptor-lpa6
#16
Reiya Taniguchi, Asuka Inoue, Misa Sayama, Akiharu Uwamizu, Keitaro Yamashita, Kunio Hirata, Masahito Yoshida, Yoshiki Tanaka, Hideaki E Kato, Yoshiko Nakada-Nakura, Yuko Otani, Tomohiro Nishizawa, Takayuki Doi, Tomohiko Ohwada, Ryuichiro Ishitani, Junken Aoki, Osamu Nureki
Lysophosphatidic acid (LPA) is a bioactive lipid composed of a phosphate group, a glycerol backbone, and a single acyl chain that varies in length and saturation. LPA activates six class A G-protein-coupled receptors to provoke various cellular reactions. Because LPA signalling has been implicated in cancer and fibrosis, the LPA receptors are regarded as promising drug targets. The six LPA receptors are subdivided into the endothelial differentiation gene (EDG) family (LPA1-LPA3) and the phylogenetically distant non-EDG family (LPA4-LPA6)...
August 17, 2017: Nature
https://www.readbyqxmd.com/read/28782946/synergistic-tailoring-of-electrostatic-and-hydrophobic-interactions-for-rapid-and-specific-recognition-of-lysophosphatidic-acid-an-early-stage-ovarian-cancer-biomarker
#17
Ying Wang, Hanwen Pei, Yan Jia, Jianhua Liu, Zelun Li, Kelong Ai, Zhongyuan Lu, Lehui Lu
Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change...
August 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28743508/design-synthesis-docking-and-biological-evaluation-of-4-phenyl-thiazole-derivatives-as-autotaxin-atx-inhibitors
#18
Anand Balupuri, Dae-Yon Lee, Myeong Hwi Lee, Sangeun Chae, Eunmi Jung, Yunki Kim, Jeonghee Ryu, Nam Sook Kang
The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is involved in several human diseases such as cancer, autoimmune diseases, inflammatory diseases neurodegenerative diseases and fibrotic diseases. Herein, a series of 4-phenyl-thiazole based compounds was designed and synthesized. Compounds were evaluated for their ATX inhibitory activity using FS-3 and human plasma assays. In the FS-3 assay, compounds 20 and 21 significantly inhibited the ATX at low nanomolar level (IC50=2.99 and 2.19nM, respectively)...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28735625/free-fatty-acid-receptor-ffar-agonists-inhibit-proliferation-of-human-ovarian-cancer-cells
#19
Mandi M Hopkins, Kathryn E Meier
Many cellular actions of omega-3 fatty acids are mediated by two G protein-coupled receptors, FFA1 and FFA4, free fatty acid receptor (FFAR) family members that are activated by these dietary constituents. FFAR agonists inhibit proliferation of human prostate and breast cancer cells. Since omega-3 fatty acids can inhibit ovarian cancer cell growth, the current study tested the potential role of FFARs in the response. OVCAR3 and SKOV3 human ovarian cancer cell lines express mRNA for FFA1; FFA4 mRNA was detected at low levels in SKOV3 but not OVCAR3...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28732508/lysophosphatidic-acid-plasma-concentrations-in-healthy-subjects-circadian-rhythm-and-associations-with-demographic-anthropometric-and-biochemical-parameters
#20
Anna Michalczyk, Marta Budkowska, Barbara Dołęgowska, Dariusz Chlubek, Krzysztof Safranow
BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive lipid with a wide biological activity. Previous studies have shown its potential usefulness as a diagnostic marker for ovarian cancer. The aim of the study was to investigate which factors may influence plasma LPA concentrations in healthy subjects and to propose reference values. METHODS: The study group consisted of 100 healthy subjects. From all of them the blood samples were taken at 7 a.m. (fasting state)...
July 21, 2017: Lipids in Health and Disease
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