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https://www.readbyqxmd.com/read/28616586/the-autotaxin-lysophosphatidic-acid-pathway-emerges-as-a-therapeutic-target-to-prevent-liver-cancer
#1
Derek J Erstad, Andrew M Tager, Yujin Hoshida, Bryan C Fuchs
Using transcriptome meta-analysis, we recently identified the autotaxin (ATX)-lysophosphatidic acid (LPA) pathway as a regulator of hepatocellular carcinoma (HCC) risk in human cirrhosis patients. Pharmacological targeting of this pathway reduced fibrosis progression and HCC development in animals, identifying ATX-LPA signaling as a novel chemoprevention strategy for cirrhosis and HCC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28591560/implications-of-the-lysophosphatidic-acid-signaling-axis-in-liver-cancer
#2
REVIEW
Chiara Lopane, Pasquale Agosti, Isabella Gigante, Carlo Sabbà, Antonio Mazzocca
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in western countries. The major risk factors for HCC are hepatitis C or B viruses, alcohol and metabolic disorders. The increasing risk of HCC in patients with metabolic disorders (i.e. obesity, diabetes and non-alcoholic steatohepatitis/NASH) regardless of the presence of liver cirrhosis is becoming relevant. Nevertheless, molecular mechanisms linking these risk factors to liver oncogenesis are unclear. This review focuses on the pathogenic role of the lysophosphatidic acid (LPA) pathway in HCC, highlighting the implications of this bioactive phospholipid in liver cancer biology and metabolism and as potential therapeutic target...
June 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28539367/implications-for-breast-cancer-treatment-from-increased-autotaxin-production-in-adipose-tissue-after-radiotherapy
#3
Guanmin Meng, Xiaoyun Tang, Zelei Yang, Matthew G K Benesch, Alison Marshall, David Murray, Denise G Hemmings, Frank Wuest, Todd P W McMullen, David N Brindley
We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy...
May 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#4
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...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447479/autotaxin-inhibitors-a-patent-review-2012-2016
#5
REVIEW
Aikaterini Nikolaou, Maroula G Kokotou, Dimitris Limnios, Anastasia Psarra, George Kokotos
Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline. The ATX/LPA axis has received increasing interest in recent years because both the enzyme ATX and the bioactive lipid LPA are involved in various pathological conditions such as tumor progression and metastasis, fibrotic diseases, autoimmune diseases, arthritis, chronic hepatitis, obesity and impaired glucose homeostasis. Thus, a great effort has been devotd in developing synthetic ATX inhibitors as new agents to treat various diseases including cancer and fibrotic diseases...
July 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28392399/preparation-of-functional-human-lysophosphatidic-acid-receptor-2-using-a-p9-%C3%A2-expression-system-and-an-amphipathic-polymer-and-investigation-of-its-in%C3%A2-vitro-binding-preference-to-g%C3%AE-proteins
#6
Seong-Gu Han, Seung-Il Baek, Tae Jin Son, Hyeongjin Lee, Nam Hyuk Kim, Yeon Gyu Yu
Human lysophosphatidic acid receptor 2 (LPA2), a member of the G-protein coupled receptor family, mediates lysophosphatidic acid (LPA)-dependent signaling by recruiting various G proteins. Particularly, it is directly implicated in the progression of colorectal and ovarian cancer through G protein signaling cascades. To investigate the biochemical binding properties of LPA2 against various alpha subunits of G protein (Gα), a functional recombinant LPA2 was overexpressed in E. coli membrane with a P9(∗) expression system, and the purified protein was stabilized with an amphipathic polymer that had been synthesized by coupling octylamine, glucosamine, and diethyl aminoproylamine at the carboxylic groups of poly-γ-glutamic acid...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28369552/youth-s-adjustment-to-cancer-examination-of-patterns-of-adjustment-and-the-role-of-peer-relations
#7
Rachel Tillery, Robert Cohen, Kristoffer S Berlin, Alanna Long, Sean Phipps
Examine unique forms of peer relations (i.e., peer group vs. friendships) in relation to patterns of youth's resilience and challenge-related growth in the context of cancer. In all, 279 youth (cancer, n  = 156; control, n  = 123) completed measures of posttraumatic stress, depression, anxiety, posttraumatic growth (PTG), and perceived positive changes. Youth also reported on their peer relations. Latent profile analysis (LPA) was used to examine patterns of youth's adjustment. Peer relations were examined as predictors of youth's adjustment...
March 22, 2017: Journal of Pediatric Psychology
https://www.readbyqxmd.com/read/28359316/evaluation-of-pancreatic-cancer-cell-migration-with-multiple-parameters-in-vitro-by-using-an-optical-real-time-cell-mobility-assay-device
#8
Akira Yamauchi, Masahiro Yamamura, Naoki Katase, Masumi Itadani, Naoko Okada, Kayoko Kobiki, Masafumi Nakamura, Yoshiyuki Yamaguchi, Futoshi Kuribayashi
BACKGROUND: Migration of cancer cell correlates with distant metastasis and local invasion, which are good targets for cancer treatment. An optically accessible device "TAXIScan" was developed, which provides considerably more information regarding the cellular dynamics and less quantity of samples than do the existing methods. Here, we report the establishment of a system to analyze the nature of pancreatic cancer cells using TAXIScan and we evaluated lysophosphatidic acid (LPA)-elicited pancreatic cell migration...
March 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28344158/laparoscopic-vs-open-approach-for-transverse-colon-cancer-a-systematic-review-and-meta-analysis-of-short-and-long-term-outcomes
#9
REVIEW
Christos D Athanasiou, Jonathan Robinson, Marina Yiasemidou, Sonia Lockwood, Georgios A Markides
BACKGROUND: Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparoscopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes...
March 24, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28342860/functional-characterization-of-lysophosphatidic-acid-receptor-1-mutants-identified-in-rat-cancer-tissues
#10
Shoichi Ishii, Toshifumi Tsujiuchi, Nobuyuki Fukushima
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28328321/ultrafast-and-predictive-mass-spectrometry-based-autotaxin-assays-for-label-free-potency-screening
#11
Tom Bretschneider, Andreas Harald Luippold, Helmut Romig, Daniel Bischoff, Klaus Klinder, Paul Nicklin, Wolfgang Rist
Autotaxin (ATX) is a promising drug target for the treatment of several diseases, such as cancer and fibrosis. ATX hydrolyzes lysophosphatidyl choline (LPC) into bioactive lysophosphatidic acid (LPA). The potency of ATX inhibitors can be readily determined by using fluorescence-based LPC derivatives. While such assays are ultra-high throughput, they are prone to false positives compared to assays based on natural LPC. Here we report the development of ultrafast mass spectrometry-based ATX assays enabling the measurement of data points within 13 s, which is 10 times faster than classic liquid chromatography-mass spectrometry...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28236660/gene-regulatory-networking-reveals-the-molecular-cue-to-lysophosphatidic-acid-induced-metabolic-adaptations-in-ovarian-cancer-cells
#12
Upasana Ray, Shreya Roy Chowdhury, Madavan Vasudevan, Kiran Bankar, Susanta Roychoudhury, Sib Sankar Roy
Extravasation and metastatic progression are two main reasons for the high mortality rate associated with cancer. The metastatic potential of cancer cells depends on a plethora of metabolic challenges prevailing within the tumor microenvironment. To achieve higher rates of proliferation, cancer cells reprogram their metabolism, increasing glycolysis and biosynthetic activities. Just why this metabolic reprogramming predisposes cells towards increased oncogenesis remains elusive. The accumulation of myriad oncolipids in the tumor microenvironment has been shown to promote the invasiveness of cancer cells, with lysophosphatidic acid (LPA) being one such critical factor enriched in ovarian cancer patients...
February 25, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28214851/lysophosphatidic-acid-promotes-epithelial-to-mesenchymal-transition-in-ovarian-cancer-cells-by-repressing-sirt1
#13
Upasana Ray, Sib Sankar Roy, Shreya Roy Chowdhury
BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) plays an essential role in the transition from early to invasive phenotype, however the underlying mechanisms still remain elusive. Herein, we propose a mechanism through which the class-III deacetylase SIRT1 regulates EMT in ovarian cancer (OC) cells. METHODS: Expression analysis was performed using Q-PCR, western blot, immunofluorescence and fluorescence-IHC study. Matrigel invasion assay was used for the invasion study...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28206976/lipid-and-alzheimer-s-disease-genes-associated-with-healthy-aging-and-longevity-in-healthy-oldest-old
#14
Lauren C Tindale, Stephen Leach, John J Spinelli, Angela R Brooks-Wilson
Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205098/enhanced-cellular-functions-through-induction-of-lpa2-by-cisplatin-in-fibrosarcoma-ht1080-cells
#15
Kaede Takahashi, Kaori Fukushima, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is a simple biophysical lipid which interacts with at least six subtypes of G protein-coupled LPA receptors (LPA1-LPA6). In cancer cells, LPA signaling via LPA receptors is involved in the regulation of malignant properties, such as cell growth, motility, and invasion. The aim of this study was to assess whether LPA receptors regulate cellular functions of fibrosarcoma cells treated with anticancer drug. HT1080 cells were maintained by the stepwise treatment of cisplatin (CDDP) at a range of 0...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28186980/diet-induced-obesity-links-to-er-positive-breast-cancer-progression-via-lpa-pkd-1-cd36-signaling-mediated-microvascular-remodeling
#16
Liuyi Dong, Ye Yuan, Cynthia Opansky, Yiliang Chen, Irene Aguilera-Barrantes, Shiyong Wu, Rong Yuan, Qi Cao, Yee Chung Cheng, Daisy Sahoo, Roy L Silverstein, Bin Ren
Obesity increases cancer risk including breast cancer (BC). However, the direct regulatory mechanisms by which obesity promotes BC progression remain largely unknown. We show that lysophosphatidic acid/protein kinase D1 (LPA/PKD-1)-CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (DIO). We observed that the growth of an estrogen receptor (ER) positive breast cancer was markedly increased when compared to the lean control, and specifically accompanied by increased microvascular remodeling in a syngeneic BC model in female DIO mice...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#17
Michelle J Farquhar, Isla S Humphreys, Simon A Rudge, Garrick K Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M Reynolds, Margaret Ashcroft, Peter Balfe, Thomas F Baumert, Stephanie Roessler, Michael J O Wakelam, Jane A McKeating
BACKGROUND & AIMS: Chronic hepatitis C is a global health problem with an estimated 170 million hepatitis C virus (HCV) infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX, gene name: ENPP2) is a phospholipase with diverse roles in the physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood...
January 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28112925/highly-potent-non-carboxylic-acid-autotaxin-inhibitors-reduce-melanoma-metastasis-and-chemotherapeutic-resistance-of-breast-cancer-stem-cells
#18
Souvik Banerjee, Derek D Norman, Sue Chin Lee, Abby L Parrill, Truc Chi T Pham, Daniel L Baker, Gabor J Tigyi, Duane D Miller
Autotaxin (ATX, aka. ENPP2) is the main source of the lipid mediator lysophosphatidic acid (LPA) in biological fluids. This study reports on inhibitors of ATX derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provide a comprehensive structure-activity relationship of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. The three most potent analogues (3a, IC50 ∼ 32 nM; 3b, IC50 ∼ 9 nM; and 14, IC50 ∼ 35 nM) inhibit ATX-dependent invasion of A2058 human melanoma cells in vitro...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28069607/lysophosphatidic-acid-converts-monocytes-into-macrophages-in-both-mice-and-humans
#19
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
#20
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
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