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Lysyl oxidase-like 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
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
Mahmut Asfuroglu, Busranur Cavdarli, Ozlem G Koz, Ahmet A Yarangumeli, Emine Y Ozdemir
PURPOSE: To investigate the genetic association of lysyl oxidase-like 1 (LOXL1) gene polymorphisms in patients with pseudoexfoliation (PEX) syndrome and PEX glaucoma of Turkish descent. METHODS: Three LOXL1 single nucleotide polymorphisms (SNPs) (rs1048661, rs3825942, and rs2165241) were analyzed in 109 Turkish patients (44 patients with PEX syndrome, 65 patients with PEX glaucoma) and 47 healthy subjects. RESULTS: "A" allele of SNP rs3825942 was underrepresented in control group compared with the glaucoma [odds ratio (OR)=4...
October 6, 2016: Journal of Glaucoma
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
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
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
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
No abstract text is available yet for this article.
July 7, 2016: Molecular Cell
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
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
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
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
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
Ralf Weiskirchen, Frank Tacke
Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltration by immune cells (especially macrophages) and increase of matrix-expressing cell types. These processes might lead to cirrhosis representing the end-stage of fibrosis. Recent clinical studies comprising patients successfully treated for viral hepatitis showed that liver fibrogenesis and even cirrhosis may be reverted...
2016: Digestive Diseases
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
Miriam Gross-Cohen, Sari Feld, Ilana Doweck, Gera Neufeld, Peleg Hasson, Gil Arvatz, Uri Barash, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor...
May 1, 2016: Cancer Research
Akira Kurozumi, Mayuko Kato, Yusuke Goto, Ryosuke Matsushita, Rika Nishikawa, Atsushi Okato, Ichiro Fukumoto, Tomohiko Ichikawa, Naohiko Seki
Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis...
May 2016: International Journal of Oncology
Z M Huang, S H Du, L G Huang, J H Li, L Xiao, P Tong
OBJECTIVE: Leptin has been found highly expressed in human osteoarthritis. We aimed to explore the possible effects and mechanisms of leptin on the apoptosis and autophagy of chondrocytes during osteoarthritis pathogenesis. METHODS: Gene expression profile from osteoarthritis affected and preserved cartilage were downloaded from NCBI's Gene Expression Omnibus database (GSE57218). Lysyl oxidase-like 3 (LOXL3) mRNA expression in cartilage tissues and leptin concentration in joint synovial fluid (SF) was measured in samples from 45 osteoarthritis patients and 25 healthy donors by real-time PCR and radioimmunoassay, respectively...
July 2016: Osteoarthritis and Cartilage
Nathan Kow, Beri Ridgeway, Mei Kuang, Robert S Butler, Margot S Damaser
OBJECTIVES: This study aimed to compare cellular expression of lysyl oxidase-like 1 (LOXL1), a key enzyme in elastin metabolism, of premenopausal women with pelvic organ prolapse (POP) compared with premenopausal controls without POP and postmenopausal women with POP. In addition, we examined whether variation of LOXL1 expression was dependent on biopsy site. METHODS: A standardized protocol was utilized to obtain vaginal biopsies from 30 women (10 premenopausal POP, 10 postmenopausal POP, and 10 premenopausal non-POP)...
July 2016: Female Pelvic Medicine & Reconstructive Surgery
Joel Rosenbloom, Shumei Ren, Edward Macarak
Fibrotic diseases constitute a world-wide major health problem, but research support remains inadequate in comparison to the need. Although considerable understanding of the pathogenesis of fibrotic reactions has been attained, no completely effective therapies exist. Although fibrotic disorders are diverse, it is universally appreciated that a particular cell type with unique characteristics, the myofibroblast, is responsible for replacement of functioning tissue with non-functional scar tissue. Understanding the cellular and molecular mechanisms responsible for the creation of myofibroblasts and their activities is central to the development of therapies...
April 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Suzan Guven Yilmaz, Melis Palamar, Huseyin Onay, Orhan Ilim, Ayca Aykut, Feristah Ferda Ozkinay, Ayse Yagci
The purpose of this study is to evaluate whole lysyl oxidase like 1 (LOXL1) gene by sequence analysis in Turkish patients with exfoliation glaucoma (XFG). A total of 48 (35 male, 13 female) patients with XFG were enrolled. Besides routine ophthalmological examination, peripapillary retinal nerve fibre layer (RNFL) analysis with optic coherence tomography was performed. Blood samples of 2 ml with EDTA were obtained and sent to Medical Genetics Department, Molecular Genetics Laboratory for LOXL1 polymorphism (PCR and agarose gel imaging) analysis...
October 2016: International Ophthalmology
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