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LPA Cancer

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https://www.readbyqxmd.com/read/28069607/lysophosphatidic-acid-converts-monocytes-into-macrophages-in-both-mice-and-humans
#1
Rashmi Ray, Vivek Rai
Monocytes and macrophages represent critical arms of the innate immune system and are considered regulators and effectors of inflammation and innate immune response. Monocytes can mobilize from bone marrow, traffic to their required destination and differentiate into effector cells depending on the local tissue environment to perform multiple roles during infection or inflammation, making them an important component of body's immune defense. Macrophages have diverse roles in tissue homeostasis, development as well as tissue repair following injury...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28058100/non-mucinous-lepidic-predominant-adenocarcinoma-presenting-with-extensive-aerogenous-spread
#2
Yusuke Takanashi, Shogo Tajima, Masaru Tsukui, Kazuya Shinmura, Takamitsu Hayakawa, Tsuyoshi Takahashi, Hiroshi Neyatani, Kazuhito Funai
An extremely rare case of non-mucinous lepidic-predominant invasive adenocarcinoma (LPA) showing extensive aerogenous spread with a pneumonic presentation is reported. A 73-year-old woman was referred to our hospital because of an infiltrative shadow on chest xray. Chest computed tomography revealed extensive ground glass opacities in the right lower lobe, which was accompanied by infiltrative shadow with a pneumonic presentation. Invasive mucinous adenocarcinoma was presumed, and a partial resection of the right lower lobe was done...
November 17, 2016: Rare Tumors
https://www.readbyqxmd.com/read/28028053/mrtf-potentiates-tead-yap-transcriptional-activity-causing-metastasis
#3
Tackhoon Kim, Daehee Hwang, Dahye Lee, Jeong-Hwan Kim, Seon-Young Kim, Dae-Sik Lim
Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity...
December 27, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28007139/phenotypic-characterization-of-genetically%C3%A2-lowered-human-lipoprotein-a-levels
#4
Connor A Emdin, Amit V Khera, Pradeep Natarajan, Derek Klarin, Hong-Hee Won, Gina M Peloso, Nathan O Stitziel, Akihiro Nomura, Seyedeh M Zekavat, Alexander G Bick, Namrata Gupta, Rosanna Asselta, Stefano Duga, Piera Angelica Merlini, Adolfo Correa, Thorsten Kessler, James G Wilson, Matthew J Bown, Alistair S Hall, Peter S Braund, Nilesh J Samani, Heribert Schunkert, Jaume Marrugat, Roberto Elosua, Ruth McPherson, Martin Farrall, Hugh Watkins, Cristen Willer, Gonçalo R Abecasis, Janine F Felix, Ramachandran S Vasan, Eric Lander, Daniel J Rader, John Danesh, Diego Ardissino, Stacey Gabriel, Danish Saleheen, Sekar Kathiresan
BACKGROUND: Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) levels has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation. OBJECTIVES: The goal of this study was to establish the full phenotypic impact of LPA gene variation and to estimate a dose-response curve between genetically altered plasma Lp(a) and risk for CHD...
December 27, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27993681/lysophosphatidic-acid-lpa-signaling-via-lpa4-and-lpa6-negatively-regulates-cell-motile-activities-of-colon-cancer-cells
#5
Kaede Takahashi, Kaori Fukushima, Yuka Onishi, Karin Inui, Yusuke Node, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27982588/structure-activity-relationships-of-small-molecule-autotaxin-inhibitors-with-a-discrete-binding-mode
#6
Lisa M Miller, Willem-Jan Keune, Diana Castagna, Louise C Young, Emma L Duffy, Frances Potjewyd, Fernando Salgado-Polo, Paloma Engel García, Dima Semaan, John M Pritchard, Anastassis Perrakis, Simon J F Macdonald, Craig Jamieson, Allan J B Watson
Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signaling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, among others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold...
January 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27981605/hepatocyte-autotaxin-expression-promotes-liver-fibrosis-and-cancer
#7
Eleanna Kaffe, Aggeliki Katsifa, Nikos Xylourgidis, Ioanna Ninou, Markella Zannikou, Vaggelis Harokopos, Pelagia Foka, Alexios Dimitriadis, Kostas Evangelou, Anargyros N Moulas, Urania Georgopoulou, Vassilis G Gorgoulis, George N Dalekos, Vassilis Aidinis
: Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the production of lysophosphatidic acid (LPA), a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver diseases (CLDs) patients of different etiologies, associated with shorter overall survival...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27888146/a-rhodium-iii-based-inhibitor-of-autotaxin-with-antiproliferative-activity
#8
Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Jia-Xin Liang, Chung-Nga Ko, Jin-Jian Lu, Xiu-Ping Chen, Dik-Lung Ma, Chung-Hang Leung
BACKGROUND: Cancer of the skin is by far the most common of all cancers. Melanoma accounts for only about 1% of skin cancers but causes a large majority of skin cancer deaths. Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), regulates physiological and pathological functions of lysophosphatidic acid (LPA), and is thus an important therapeutic target. METHODS: We synthesized ten metal-based complexes and a novel cyclometalated rhodium(III) complex 1 was identified as an ATX enzymatic inhibitor using multiple methods, including ATX enzymatic assay, thermal shift assay, western immunoblotting and so on...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27864940/endogenous-lysophosphatidic-acid-lpa1-receptor-agonists-demonstrate-ligand-bias-between-calcium-and-erk-signalling-pathways-in-human-lung-fibroblasts
#9
Afrah Sattikar, Mark R Dowling, Elizabeth M Rosethorne
BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins. This promiscuity of coupling raises the possibility that some of the LPA analogues may bias the LPA1 receptor towards one signalling pathway over another...
February 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27809800/lpa-receptor-1-mediates-lpa-induced-ovarian-cancer-metastasis-an-in-vitro-and-in-vivo-study
#10
Xuechen Yu, Yuanzhen Zhang, Huijun Chen
BACKGROUND: The facts that LPA is present at high concentration in ovarian cancer patients' ascites and it may serve as a stimulator to cell migration, implicate the role of LPA in the ovarian cancer metastasis. Since LPA mediates various biological functions through its interaction with LPA receptors, we aim to investigate the correlation between the expression of LPA receptors and the metastasis of ovarian cancer. METHODS: To test whether the LPA responsiveness correlated with the metastatic capability of ovarian cancer cells, we performed LPA induced invasion assay and peritoneal metastatic colonization assay with a panel of established human ovarian cancer cell lines...
November 4, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27808166/lpa-receptor-activity-is-basal-specific-and-coincident-with-early-pregnancy-and-involution-during-mammary-gland-postnatal-development
#11
Deanna Acosta, Susmita Bagchi, Pilib Ó Broin, Daniel Hollern, Silvia E Racedo, Bernice Morrow, Rani S Sellers, John M Greally, Aaron Golden, Eran Andrechek, Teresa Wood, Cristina Montagna
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784781/autotaxin-expression-is-regulated-at-the-post-transcriptional-level-by-the-rna-binding-proteins-hur-and-auf1
#12
Shuhong Sun, Xiaotian Zhang, Lin Lyu, Xixi Li, Siliang Yao, Junjie Zhang
Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a lysophospholipid mediator that regulates cellular activities through its specific G protein-coupled receptors. The ATX-LPA axis plays an important role in various physiological and pathological processes, especially in inflammation and cancer development. Although the transcriptional regulation of ATX has been widely studied, the post-transcriptional regulation of ATX is largely unknown. In this study, we identified conserved adenylate-uridylate (AU)-rich elements in the ATX mRNA 3'-untranslated region (3'UTR)...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27780817/reallocating-time-to-sleep-sedentary-time-or-physical-activity-associations-with-waist-circumference-and-body-mass-index-in-breast-cancer-survivors
#13
Terry Boyle, Jeff K Vallance, Matthew Buman, Brigid M Lynch
BACKGROUND: Moderate-to-vigorous intensity physical activity (MVPA) is inversely associated with waist circumference and body mass index (BMI) among breast cancer survivors. Limited research has focused on behaviours that account for larger portions of the day [sleep, sedentary time, and light-intensity physical activity (LPA)]. We investigated the interdependent associations of self-reported sleep, objectively-assessed prolonged and short bouts of sedentary time, total LPA and total MVPA with waist circumference and BMI...
October 25, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27780639/discovery-of-potent-inhibitors-of-the-lysophospholipase-autotaxin
#14
Pritom Shah, Anne Cheasty, Caroline Foxton, Tony Raynham, Muddasar Farooq, Irene Farre Gutierrez, Aurore Lejeune, Michelle Pritchard, Andrew Turnbull, Leon Pang, Paul Owen, Susan Boyd, Alexandra Stowell, Allan Jordan, Niall M Hamilton, James R Hitchin, Martin Stockley, Ellen MacDonald, Mar Jimenez Quesada, Elisabeth Trivier, Jana Skeete, Huib Ovaa, Wouter H Moolenaar, Hamish Ryder
The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27767105/monoacylglycerol-lipase-a-novel-potential-therapeutic-target-and-prognostic-indicator-for-hepatocellular-carcinoma
#15
Junyong Zhang, Zuojin Liu, Zhengrong Lian, Rui Liao, Yi Chen, Yi Qin, Jinlong Wang, Qing Jiang, Xiaobo Wang, Jianping Gong
Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27757783/overexpression-of-autotaxin-is-associated-with-human-renal-cell-carcinoma-and-bladder-carcinoma-and-their-progression
#16
Aihua Xu, Md Ahsanul Kabir Khan, Fangzhi Chen, Zhaohui Zhong, Han-Chun Chen, Yuanda Song
Autotaxin (ATX) as an important tumor cell motility-stimulating factor is upregulated in many different types of cancer. ATX, a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, possesses lysophospholipase D activity which hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and mitogen lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors, thereby regulating cell growth, migration, and survival. This study aimed to investigate the differences in gene expression pattern of ATX between cancerous and adjacent normal tissue of human renal cell carcinoma (RCC) and bladder carcinoma (BC) and find the correlation between ATX expression and clinicopathological features of both of these carcinomas...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27644846/roles-of-lpa-receptor-signaling-in-breast-cancer
#17
Jizhao Wang, Yuchen Sun, Jingkun Qu, Yan Yan, Ya Yang, Hui Cai
LPA and its receptors play an important role in mediating malignant behaviors in various cancers, including breast cancer. Aberrant expression of certain LPA receptors in breast cancer suggested that LPA receptors could be potential biomarkers in understanding malignant growth patterns of breast cancer. Further research considering molecular mechanisms for LPA receptors will contribute to new methods of malignant breast cancer diagnosis and treatment. Areas covered: Accumulating studies have indicated that LPA receptors correlated to proliferation, invasion, migration and metastasis both in vivo and in vitro...
October 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27631681/modulation-of-nav1-8-by-lysophosphatidic-acid-in-the-induction-of-bone-cancer-pain
#18
Hai-Li Pan, Ben-Long Liu, Wei Lin, Yu-Qiu Zhang
Given that lysophosphatidic acid (LPA) and the tetrodotoxin-resistant sodium channel Nav1.8 are both involved in bone cancer pain, the present study was designed to investigate whether crosstalk between the LPA receptor LPA1 (also known as EDG2) and Nav1.8 in the dorsal root ganglion (DRG) contributes to the induction of bone cancer pain. We showed that the EDG2 antagonist Ki16198 blocked the mechanical allodynia induced by intrathecal LPA in naïve rats and attenuated mechanical allodynia in a rat model of bone cancer...
October 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27597281/microenvironmental-changes-in-the-progression-from-adenocarcinoma-in-situ-to-minimally-invasive-adenocarcinoma-and-invasive-lepidic-predominant-adenocarcinoma-of-the-lung
#19
Masahito Naito, Keiju Aokage, Kouichi Saruwatari, Kakeru Hisakane, Tomohiro Miyoshi, Tomoyuki Hishida, Junji Yoshida, Sugano Masato, Motohiro Kojima, Takeshi Kuwata, Satoshi Fujii, Atsushi Ochiai, Yukitoshi Sato, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. MATERIALS AND METHODS: Clinicopathological characteristics of AIS (n=51), MIA (n=59), LPA smaller than 3cm (LPA-S, n=113), and LPA larger than 3cm (LPA-L, n=47) were analyzed...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27596548/-correlation-analysis-between-glycolipids-metabolism-and-clinicopathologic-features-in-patients-with-gastric-cancer
#20
T Zhang, G Cui, W M Feng, Q L Shi, J Cui, X N Li, Q C Wang, H Shen
OBJECTIVE: To analyze the correlation between glycolipids metabolism and clinicopathologic features in patients with gastric cancer. METHODS: Glycolipids metabolism and clinicopathologic features of 443 gastric cancer patients were collected, and their correlation was analyzed. RESULTS: Compared to gastric cancer patients with normal levels of glycolipids metabolism, there were less male patients who were with low level of total cholesterol (TCH)(χ(2)=7...
August 23, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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