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LPA Cancer

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
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
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
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
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
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]
Mark F McCarty, James DiNicolantonio
Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases...
August 25, 2016: Healthcare (Basel, Switzerland)
Chanida Vinayanuwattikun, Florence Le Calvez-Kelm, Behnoush Abedi-Ardekani, David Zaridze, Anush Mukeria, Catherine Voegele, Maxime Vallée, Dewajani Purnomosari, Nathalie Forey, Geoffroy Durand, Graham Byrnes, James Mckay, Paul Brennan, Ghislaine Scelo
To examine the diversity of somatic alterations and clonal evolution according to aggressiveness of disease, nineteen tumor-blood pairs of 'formerly bronchiolo-alveolar carcinoma (BAC)' which had been reclassified into preinvasive lesion (adenocarcinoma in situ; AIS), focal invasive lesion (minimally invasive adenocarcinoma; MIA), and invasive lesion (lepidic predominant adenocarcinoma; LPA and non-lepidic predominant adenocarcinoma; non-LPA) according to IASLC/ATS/ERS 2011 classification were explored by whole exome sequencing...
2016: Scientific Reports
Lauren E Ragle, Dilip J Palanisamy, Margaux J Joe, Rachel S Stein, Derek D Norman, Gabor Tigyi, Daniel L Baker, Abby L Parrill
Autotaxin (ATX) is a ubiquitous ectoenzyme that hydrolyzes lysophosphatidylcholine (LPC) to form the bioactive lipid mediator lysophosphatidic acid (LPA). LPA activates specific G-protein coupled receptors to elicit downstream effects leading to cellular motility, survival, and invasion. Through these pathways, upregulation of ATX is linked to diseases such as cancer and cardiovascular disease. Recent crystal structures confirm that the catalytic domain of ATX contains multiple binding regions including a polar active site, hydrophobic tunnel, and a hydrophobic pocket...
October 1, 2016: Bioorganic & Medicinal Chemistry
Matthew G K Benesch, Xiaoyun Tang, Ganesh Venkatraman, Raie T Bekele, David N Brindley
Extracellular lysophosphatidate (LPA) is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin (ATX), and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases (LPPs). In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low LPP activity...
July 2016: Journal of Biomedical Research
Puya Gharahkhani, Rebecca C Fitzgerald, Thomas L Vaughan, Claire Palles, Ines Gockel, Ian Tomlinson, Matthew F Buas, Andrea May, Christian Gerges, Mario Anders, Jessica Becker, Nicole Kreuser, Tania Noder, Marino Venerito, Lothar Veits, Thomas Schmidt, Hendrik Manner, Claudia Schmidt, Timo Hess, Anne C Böhmer, Jakob R Izbicki, Arnulf H Hölscher, Hauke Lang, Dietmar Lorenz, Brigitte Schumacher, Andreas Hackelsberger, Rupert Mayershofer, Oliver Pech, Yogesh Vashist, Katja Ott, Michael Vieth, Josef Weismüller, Markus M Nöthen, Stephen Attwood, Hugh Barr, Laura Chegwidden, John de Caestecker, Rebecca Harrison, Sharon B Love, David MacDonald, Paul Moayyedi, Hans Prenen, R G Peter Watson, Prasad G Iyer, Lesley A Anderson, Leslie Bernstein, Wong-Ho Chow, Laura J Hardie, Jesper Lagergren, Geoffrey Liu, Harvey A Risch, Anna H Wu, Weimin Ye, Nigel C Bird, Nicholas J Shaheen, Marilie D Gammon, Douglas A Corley, Carlos Caldas, Susanne Moebus, Michael Knapp, Wilbert H M Peters, Horst Neuhaus, Thomas Rösch, Christian Ell, Stuart MacGregor, Paul Pharoah, David C Whiteman, Janusz Jankowski, Johannes Schumacher
BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma...
October 2016: Lancet Oncology
Mandi M Hopkins, Ze Liu, Kathryn E Meier
Lysophosphatidic acid (LPA) is a lipid mediator that mediates cellular effects via G protein-coupled receptors (GPCRs). Epidermal growth factor (EGF) is a peptide that acts via a receptor tyrosine kinase. LPA and EGF both induce proliferation of prostate cancer cells and can transactivate each other's receptors. The LPA receptor LPA1 is particularly important for LPA response in human prostate cancer cells. Previous work in our laboratory has demonstrated that free fatty acid 4 (FFA4), a GPCR activated by ω-3 fatty acids, inhibits responses to both LPA and EGF in these cells...
October 2016: Journal of Pharmacology and Experimental Therapeutics
(no author information available yet)
The above article in Cancer Science (doi: 10.1111/cas.12768), published online on 26 October 2015 in Wiley Online Library (, has been retracted by agreement between the authors, the journal Editor in Chief, Yusuke Nakamura, and Wiley Publishing Asia Pty Ltd. The retraction has been agreed as Panels +C3 and +Y27632 of SW480 Mock shown in Figure 2a appear to have been taken from the same image, Panels + C3 and +Y27632 of HT29 FMNL2 shown in Figure 2a appear to have been taken from the same image, Panels shFMNL2-1 and shmDial1-1 in Figure 3a appear to have been taken from the same image, shFMNL2-2 and shmDial1-2 in Figure 3a appear to have been taken from the same image, Panels of shFMNL2-1 + shmDial1-1 and shFMNL2-1 + shmDial1-2 of +LPA appear to have been taken from the same image, gel bands of FLAG in Figure 4e appear to have been have been manipulated by erasing gel bands...
July 2016: Cancer Science
Tomoharu Yoshiya, Takahiro Mimae, Yasuhiro Tsutani, Norifumi Tsubokawa, Shinsuke Sasada, Yoshihiro Miyata, Kei Kushitani, Yukio Takeshima, Shuji Murakami, Hiroyuki Ito, Haruhiko Nakayama, Morihito Okada
BACKGROUND: The prognosis of patients with small, node-negative lung cancers, which the current indication for adjuvant chemotherapy never includes, is sometimes poor despite complete tumor resection. The present study aimed to identify independent prognostic factors and to clarify possible candidates for adjuvant chemotherapy among patients with small, node-negative invasive adenocarcinoma. METHODS: This study involved 153 patients with completely resected small (≤20 mm) pathologic N0 invasive adenocarcinomas...
June 23, 2016: Annals of Thoracic Surgery
Jung-Min Lee, Soo-Jin Park, Dong-Soon Im
Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca(2+) through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA1 antagonists showed LPE induced intracellular Ca(2+) increases in an LPA1 GPCR-dependent manner...
June 17, 2016: Biomolecules & Therapeutics
Lian-Mei Zhao, Guo-Gui Sun, Li-Na Han, Li-Hua Liu, Feng-Zhi Ren, Lei Li, Ming Ma, Bao-En Shan
BACKGROUND/AIMS: Due to its antitumor and gastroprotective properties, cochinchina momordica seed (CMS), has been widely used to treat cancer patients in Asia. Our previous reports have shown that CMS is able to induce the differentiation of B16-F1 melanoma cells. However, its functional component and mechanism remain unclear and are addressed in this study. METHODS AND RESULTS: CMSP (p-hydroxycinnamaldehyde isolated from CMS) inhibited the proliferation, migration and invasiveness of B16-F1 cells both in vivo and in vitro...
2016: Cellular Physiology and Biochemistry
Ji Hee Ha, Jeremy D Ward, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Yong Sang Song, Danny N Dhanasekaran
Recent studies have identified a critical role for lysophosphatidic acid (LPA) in the progression of ovarian cancer. Using a transcription factor activation reporter array, which analyzes 45 distinct transcription factors, it has been observed that LPA observed robustly activates the transcription factor hypoxia-induced factor-1α (HIF1α) in SKOV3.ip ovarian cancer cells. HIF1α showed 150-fold increase in its activation profile compared to the untreated control. Validation of the array analysis indicated that LPA stimulates a rapid increase in the levels of HIF1α in ovarian cancer cells, with an observed maximum level of HIF1α-induction by 4 hours...
May 7, 2016: Oncotarget
Felix Hövelmann, Katarzyna M Kedziora, André Nadler, Rainer Müller, Kees Jalink, Carsten Schultz
Lysophosphatidic acid (LPA) is a serum-borne lipid mediator that binds to a variety of different G protein-coupled receptors to trigger an exceptionally wide range of biological effects, including cell survival and differentiation, cancer cell migration, and embryonic development. Here we synthesized caged LPA (cgLPA), a "photolysable" coumarin-masked derivative of LPA. We demonstrate that illumination of cgLPA with 405 nm light liberates bioactive LPA on a subsecond scale to evoke Ca(2+) signaling, Rho activation, and cytoskeletal contraction...
May 19, 2016: Cell Chemical Biology
Michihiro Yoshida, Peijian He, C Chris Yun
Lysophosphatidic acid (LPA) acts on LPA2 receptor to mediate multiple pathological effects that are associated with tumorigenesis. The absence of LPA2 attenuates tumor progression in rodent models of colorectal cancer, but whether overexpression of LPA2 alone can lead to malignant transformation in the intestinal tract has not been studied. In this study, we expressed human LPA2 in intestinal epithelial cells (IECs) under control of the villin promoter. Less than 4% of F1-generation mice had germline transmission of transgenic (TG) human LPA2; as such only 3 F1 mice out of 72 genotyped had TG expression...
2016: PloS One
William D Travis, Hisao Asamura, Alexander A Bankier, Mary Beth Beasley, Frank Detterbeck, Douglas B Flieder, Jin Mo Goo, Heber MacMahon, David Naidich, Andrew G Nicholson, Charles A Powell, Mathias Prokop, Ramón Rami-Porta, Valerie Rusch, Paul van Schil, Yasushi Yatabe
This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS)...
August 2016: Journal of Thoracic Oncology
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