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LOXL2

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https://www.readbyqxmd.com/read/27869162/the-histone-demethylase-kdm4b-regulates-peritoneal-seeding-of-ovarian-cancer
#1
C Wilson, L Qiu, Y Hong, T Karnik, G Tadros, B Mau, T Ma, Y Mu, J New, R J Louie, S Gunewardena, A K Godwin, O W Tawfik, J Chien, K F Roby, A J Krieg
Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because of widespread dissemination of peritoneal metastases at diagnosis. Multiple pathways contribute to the aggressiveness of ovarian cancer, including hypoxic signaling mechanisms. In this study, we have determined that the hypoxia-inducible histone demethylase KDM4B is expressed in ∼60% of EOC tumors assayed, including primary and matched metastatic tumors. Expression of KDM4B in tumors is positively correlated with expression of the tumor hypoxia marker CA-IX, and is robustly induced in EOC cell lines exposed to hypoxia...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27860390/increased-lysyl-oxidase-like-2-associates-with-a-poor-prognosis-in-non-small-cell-lung-cancer
#2
Ping Zhan, Xiao-Jing Lv, Ya-Nan Ji, Haiyan Xie, Li-Ke Yu
BACKGROUND: Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and is associated with invasiveness and metastasis in breast cancer. However, its relevance in non-small cell lung cancer (NSCLC) remained largely unknown. METHODS: LOXL2 protein levels in a cohort of NSCLC and adjacent normal lung tissues were evaluated and analyzed their clinicopathologic and prognostic significance. RESULTS: We found that cytoplasmic and nuclear LOXL2 levels were higher in lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) tissues than in paired adjacent normal tissues...
November 18, 2016: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27784228/a-perspective-on-stem-cells-as-biological-systems-that-produce-differentiated-osteoblasts-and-odontoblasts
#3
Shahrul Hisham Zainal Ariffin, Thanaletchumi Manogaran, Intan Zarina Zainol Abidin, Rohaya Megat Abdul Wahab, Sahidan Senafi
Stem cells (SCs) are capable of self-renewal and multilineage differentiation. Human mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) which can be obtained from multiple sources, are suitable for application in regenerative medicine and transplant therapy. The aim of this review is to evaluate the potential of genomic and proteomic profiling analysis to identify the differentiation of MSCs and HSCs towards osteoblast and odontoblast lineages. In vitro differentiation towards both of these lineages can be induced using similar differentiation factors...
October 26, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27770022/lysyl-oxidase-like-2-crosslinks-collagen-iv-of-glomerular-basement-membrane
#4
Carolina Anazco, Alberto J Lopez-Jimenez, Mohamed Rafi, Lorenzo Vega-Montoto, Ming-Zhi Zhang, Billy G Hudson, Roberto M Vanacore
The 7S dodecamer is recognized as an important structural crosslinking domain of collagen IV networks that provide mechanical stability to basement membranes, a specialized form of extracellular matrix essential for the development and maintenance of tissue architecture. Although the 7S dodecamer is stabilized by covalent crosslinking, the molecular mechanism by which such crosslinks are formed has not been revealed. Here we aimed to identify the enzyme(s) that crosslinks the 7S dodecamer and characterize its expression in the kidney glomerulus...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27769988/influencing-the-tumor-microenvironment-phase-2-study-of-copper-depletion-with-tetrathiomolybdate-in-high-risk-breast-cancer-and-preclinical-models-of-lung-metastases
#5
Nancy Chan, Amy Willis, Naomi Kornhauser, Maureen M Ward, Sharrell B Lee, Eleni Nackos, Bo Ri Seo, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Marta Vallee Cobham, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Elnaz Anjom, Richard Zelkowitz, J David Warren, Maureen E Lane, Claudia Fischbach, Vivek Mittal, Linda Vahdat
PURPOSE: Bone marrow derived progenitor cells; including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways model the tumor microenvironment. We hypothesized that copper depletion (CD) using tetrathiomolybdate (TM) would reduce EPCs in high risk for relapse breast cancer (BC) patients (pts). We investigated the effect of TM on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Stage 2 triple negative BC (TNBC), Stage 3 and stage 4 without any evidence of disease, (NED) BC pts, received oral TM to maintain ceruloplasmin (Cp) between 8-17mg/dL for 2 years or until relapse...
October 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27735137/lysyl-oxidase-like-2-loxl2-oxidizes-trimethylated-lysine-4-in-histone-h3
#6
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Laura Pascual-Reguant, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Ane Iturbide, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
: Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene...
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27720259/tgf-%C3%AE-1-promotes-linear-invadosome-formation-in-hepatocellular-carcinoma-cells-through-ddr1-up-regulation-and-collagen-i-cross-linking
#7
Zakaria Ezzoukhry, Elodie Henriet, Léo Piquet, Kevin Boyé, Paulette Bioulac-Sage, Charles Balabaud, Gabrielle Couchy, Jessica Zucman-Rossi, Violaine Moreau, Frédéric Saltel
Transforming growth factor-β1 (TGF-β1) is an important player in chronic liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC) development. TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels. TGF-β1 was described to enhance production of type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2 (LOXL2). In addition, TGF-β1 and type I collagen are potent inducers of invadosomes. Indeed, type I collagen fibers induce the formation of active linear invadosomes through the discoidin domain receptor 1 (DDR1)...
October 4, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27694892/zeb1-induces-loxl2-mediated-collagen-stabilization-and-deposition-in-the-extracellular-matrix-to-drive-lung-cancer-invasion-and-metastasis
#8
D H Peng, C Ungewiss, P Tong, L A Byers, J Wang, J R Canales, P A Villalobos, N Uraoka, B Mino, C Behrens, I I Wistuba, R I Han, C A Wanna, M Fahrenholtz, K J Grande-Allen, C J Creighton, D L Gibbons
Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis...
October 3, 2016: Oncogene
https://www.readbyqxmd.com/read/27488440/regulation-of-loxl2-and-serpinh1-by-antitumor-microrna-29a-in-lung-cancer-with-idiopathic-pulmonary-fibrosis
#9
Kazuto Kamikawaji, Naohiko Seki, Masaki Watanabe, Hiroko Mataki, Tomohiro Kumamoto, Koichiro Takagi, Keiko Mizuno, Hiromasa Inoue
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells...
August 4, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27430160/the-effect-of-loxl2-in-hepatocellular-carcinoma
#10
Linghong Wu, Yuan Zhang, Ying Zhu, Qingwei Cong, Yan Xiang, Linlin Fu
Lysyl oxidase-like 2 (LOXL2) is key in the hepatocellular carcinoma (HCC) tumor microenvironment and metastatic niche formation. However, its effect on proliferation and clinical parameters in HCC require further elucidation. The present study aimed to investigate LOXL2 expression in HCC from in vitro and clinical aspects. The present study constructed LOXL2‑small interfering RNA with a lentiviral vector, investigated the effect of LOXL2 on proliferation using HCC cell lines via a series of assays, including reverse transcription‑quantitative polymerase chain reaction, cell counting, colony formation, assessment of cell cycle and apoptosis using flow cytometry, MTT and BrdU...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27363654/impact-of-stroma-loxl2-overexpression-on-the-prognosis-of-intrahepatic-cholangiocarcinoma
#11
Damien Bergeat, Alain Fautrel, Bruno Turlin, Aude Merdrignac, Michel Rayar, Karim Boudjema, Cédric Coulouarn, Laurent Sulpice
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC...
June 15, 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27285767/emerging-role-of-loxl2-in-the-promotion-of-pancreas-cancer-metastasis
#12
Joon Seong Park, Ji-Hae Lee, Yun Sun Lee, Jae Keun Kim, Seung Myung Dong, Dong Sup Yoon
Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in cancer. We analyzed the prognostic impact of LOXL2 in pancreatic cancer patients and investigated the role of LOXL2 in pancreatic cancer cell lines. Immunohistochemical analysis was performed in samples from 80 patients and showed LOXL2 expression in 81.2% of patients with pancreatic cancer. Regarding recurrence patterns, LOXL2-positive tumors showed a significantly higher rate of distant recurrence. The 1-year and 3-year disease-free survival rates were 84...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27278788/regulation-of-metastasis-promoting-loxl2-gene-expression-by-antitumor-micrornas-in-prostate-cancer
#13
Mayuko Kato, Akira Kurozumi, Yusuke Goto, Ryosuke Matsushita, Atsushi Okato, Rika Nishikawa, Ichiro Fukumoto, Keiichi Koshizuka, Tomohiko Ichikawa, Naohiko Seki
Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs...
June 9, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27232579/simtuzumab-treatment-of-advanced-liver-fibrosis-in-hiv-and-hcv-infected-adults-results-of-a-6-month-open-label-safety-trial
#14
Eric G Meissner, Mary McLaughlin, Lindsay Matthews, Ahmed M Gharib, Bradford J Wood, Elliot Levy, Ralph Sinkus, Kimmo Virtaneva, Dan Sturdevant, Craig Martens, Stephen F Porcella, Zachary D Goodman, Bittoo Kanwar, Robert P Myers, Mani Subramanian, Colleen Hadigan, Henry Masur, David E Kleiner, Theo Heller, Shyam Kottilil, Joseph A Kovacs, Caryn G Morse
BACKGROUND: Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. AIM: The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease...
December 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27221706/tumor-cell-invasion-can-be-blocked-by-modulators-of-collagen-fibril-alignment-that-control-assembly-of-the-extracellular-matrix
#15
Moran Grossman, Nir Ben-Chetrit, Alina Zhuravlev, Ran Afik, Elad Bassat, Inna Solomonov, Yosef Yarden, Irit Sagi
Abnormal architectures of collagen fibers in the extracellular matrix (ECM) are hallmarks of many invasive diseases, including cancer. Targeting specific stages of collagen assembly in vivo presents a great challenge due to the involvement of various crosslinking enzymes in the multistep, hierarchical process of ECM build-up. Using advanced microscopic tools, we monitored stages of fibrillary collagen assembly in a native fibroblast-derived 3D matrix system and identified anti-lysyl oxidase-like 2 (LOXL2) antibodies that alter the natural alignment and width of endogenic fibrillary collagens without affecting ECM composition...
July 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27186784/re-tumour-suppressive-microrna-29s-directly-regulate-loxl2-expression-and-inhibit-cancer-cell-migration-and-invasion-in-renal-cell-carcinoma
#16
https://www.readbyqxmd.com/read/27116380/correlation-of-aqueous-humor-lysyl-oxidase-activity-with-tgf-%C3%A3-levels-and-loxl1-genotype-in-pseudoexfoliation
#17
Ramakrishnan Gayathri, Karunakaran Coral, Ferdinamarie Sharmila, Sarangapani Sripriya, Krishnamoorthy Sripriya, Panday Manish, B Shantha, George Ronnie, Lingam Vijaya, Angayarkanni Narayanasamy
PURPOSE: Pseudoexfoliation (PXF) is a microfibrillopathy involving disordered elastogenesis. Abnormal extracellular matrix (ECM) production underlies the pathophysiology of PXF. The enzyme Lysyl oxidase (LOX) and its isoforms are known to cross-link the elastin and collagen. Though the etiopathogensis of PXF is not well understood, studies report on the genetic risk involving LOXL1 gene. This study aims to screen LOXL1 coding variants rs1048661 and rs3825942 in the South Indian population and the implication of the single nucleotide polymorphism (SNP) with LOX activity...
April 26, 2016: Current Eye Research
https://www.readbyqxmd.com/read/27063404/a-truncated-splice-variant-of-human-lysyl-oxidase-like-2-promotes-migration-and-invasion-in-esophageal-squamous-cell-carcinoma
#18
Hai-Ying Zou, Guo-Qing Lv, Li-Hua Dai, Xiu-Hui Zhan, Ji-Wei Jiao, Lian-Di Liao, Tai-Mei Zhou, Chun-Quan Li, Bing-Li Wu, Li-Yan Xu, En-Min Li
Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family, which plays an important role in extracellular matrix protein biosynthesis and tumor progression. In the present study, we identified a novel splice variant, LOXL2Δ72, which encodes a peptide having the same N- and C-termini as wild-type LOXL2 (LOXL2WT), but lacks 72 nucleotides encoding 24 amino acids. LOXL2Δ72 had dramatically reduced enzymatic activity, and was no longer secreted. However, LOXL2Δ72 promoted greater cell migration and invasion than LOXL2WT...
June 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27050073/lysyl-oxidase-family-activity-promotes-resistance-of-pancreatic-ductal-adenocarcinoma-to-chemotherapy-by-limiting-the-intratumoral-anticancer-drug-distribution
#19
Benjamin Le Calvé, Audrey Griveau, David Vindrieux, Raphaël Maréchal, Clotilde Wiel, Magali Svrcek, Johann Gout, Lamia Azzi, Léa Payen, Jérôme Cros, Christelle de la Fouchardière, Pierre Dubus, Jérôme Guitton, Laurent Bartholin, Jean-Baptiste Bachet, David Bernard
Solid tumors often display chemotherapy resistance. Pancreatic ductal adenocarcinoma (PDAC) is the archetype of resistant tumors as current chemotherapies are inefficient. The tumor stroma and extracellular matrix (ECM) are key contributors to PDAC aggressiveness and to limiting the efficacy of chemotherapy. Lysyl oxidase (LOX) family members mediate collagen cross-linking and thus promote ECM stiffening. Our data demonstrate increased LOX, LOXL1, and LOXL2 expression in PDAC, and that the level of fibrillar collagen, which is directly dependent of LOX family activity, is an independent predictive biomarker of adjuvant "Gemcitabine-based chemotherapy" benefit...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27008697/escin-ia-suppresses-the-metastasis-of-triple-negative-breast-cancer-by-inhibiting-epithelial-mesenchymal-transition-via-down-regulating-loxl2-expression
#20
Yuhui Wang, Xiaotian Xu, Peng Zhao, Bei Tong, Zhifeng Wei, Yue Dai
The saponin fraction of Aesculus chinensis Bunge fruits (SFAC) could inhibit the invasion and migration of MDA-MB-231 cells. Among which, escin Ia showed more potent inhibition of the invasion than other five main saponin constituents. It selectively reduced the expression of LOXL2 mRNA and promoted the expression of E-cadherin mRNA, and prevented the EMT process of MDA-MB-231 cells and TNF-α/TGF-β-stimulated MCF-7 cells. Moreover, it reduced the LOXL2 level in MDA-MB-231 cells but not in MCF-7 cells. When MCF-7 cells were stimulated with TNF-α/TGF-β, transfected with LOXL2 or treated with hypoxia, escin Ia down-regulated the level of LOXL2 in MCF-7 cells...
April 26, 2016: Oncotarget
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