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https://www.readbyqxmd.com/read/28705793/dachsous1-fat4-signaling-controls-endothelial-cell-polarization-during-lymphatic-valve-morphogenesis
#1
Francoise Pujol, Tina Hodgson, Ines Martinez-Corral, Anne-Catherine Prats, Danelle Devenport, Masatoshi Takeichi, Elisabeth Genot, Taija Mäkinen, Philippa Francis-West, Barbara Garmy-Susini, Florence Tatin
OBJECTIVE: The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature. APPROACH AND RESULTS: Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1(high) cells) are disoriented and failed to form proper valve leaflets...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28700469/microarray-analysis-of-copy-number-variations-and-gene-expression-profiles-in-prostate-cancer
#2
Yuping Han, Xuefei Jin, Hongyan Li, Kaichen Wang, Ji Gao, Lide Song, Yanting Lv
BACKGROUND: This study aimed to identify potential prostate cancer (PC)-related variations in gene expression profiles. METHODS: Microarray data from the GSE21032 dataset that contained the whole-transcript and exon-level expression profile (GSE21034) and Agilent 244K array-comparative genomic hybridization data (GSE21035) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and copy-number variations (CNVs) were identified between PC and normal tissue samples...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28551381/a-specific-mutational-signature-associated-with-dna-8-oxoguanine-persistence-in-mutyh-defective-colorectal-cancer
#3
Alessandra Viel, Alessandro Bruselles, Ettore Meccia, Mara Fornasarig, Michele Quaia, Vincenzo Canzonieri, Eleonora Policicchio, Emanuele Damiano Urso, Marco Agostini, Maurizio Genuardi, Emanuela Lucci-Cordisco, Tiziana Venesio, Aline Martayan, Maria Grazia Diodoro, Lupe Sanchez-Mete, Vittoria Stigliano, Filomena Mazzei, Francesca Grasso, Alessandro Giuliani, Marta Baiocchi, Roberta Maestro, Giuseppe Giannini, Marco Tartaglia, Ludmil B Alexandrov, Margherita Bignami
8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28488382/neuron-specific-knockdown-of-the-drosophila-fat-induces-reduction-of-life-span-deficient-locomotive-ability-shortening-of-motoneuron-terminal-branches-and-defects-in-axonal-targeting
#4
Aya Nakamura, Ryo Tanaka, Kazushige Morishita, Hideki Yoshida, Yujiro Higuchi, Hiroshi Takashima, Masamitsu Yamaguchi
Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system...
May 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28239148/amotl1-mediates-sequestration-of-the-hippo-effector-yap1-downstream-of-fat4-to-restrict-heart-growth
#5
Chiara V Ragni, Nicolas Diguet, Jean-François Le Garrec, Marta Novotova, Tatiana P Resende, Sorin Pop, Nicolas Charon, Laurent Guillemot, Lisa Kitasato, Caroline Badouel, Alexandre Dufour, Jean-Christophe Olivo-Marin, Alain Trouvé, Helen McNeill, Sigolène M Meilhac
Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus...
February 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28120184/application-of-unique-sequence-index-usi-barcode-to-gene-expression-profiling-in-gastric-adenocarcinoma
#6
Sadegh Fattahi, Maryam Pilehchian Langroudi, Ali Akbar Samadani, Novin Nikbakhsh, Mohsen Asouri, Haleh Akhavan-Niaki
Accurate expression profiling is imperative for understanding the biological roles of mRNAs. Real-time PCR have been at the forefront of biological innovation in detection and monitoring of gene expression, however, fluorophore-labeled oligonucleotides and double-stranded DNA binding dyes, the two most frequently used dyes in RNA detection, are not very cost effective and have poor specificity, respectively. We have developed a cost effective and specific approach for mRNA expression profiling via added unique sequence index (USI) to cDNAs before amplification...
March 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27942226/history-and-progression-of-fat-cadherins-in-health-and-disease
#7
REVIEW
Xiaofeng Zhang, Jinghua Liu, Xiao Liang, Jiang Chen, Junjie Hong, Libo Li, Qiang He, Xiujun Cai
Intercellular adhesions are vital hubs for signaling pathways during multicellular development and animal morphogenesis. In eukaryotes, under aberrant intracellular conditions, cadherins are abnormally regulated, which can result in cellular pathologies such as carcinoma, kidney disease, and autoimmune diseases. As a member of the Ca(2+)-dependent adhesion super-family, Fat proteins were first described in the 1920s as an inheritable lethal mutant phenotype in Drosophila, consisting of four member proteins, FAT1, FAT2, FAT3, and FAT4, all of which are highly conserved in structure...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27896700/fat4-functions-as-a-tumor-suppressor-in-triple-negative-breast-cancer
#8
Lingmi Hou, Maoshan Chen, Xiaobo Zhao, Jingdong Li, Shishan Deng, Jiani Hu, Hongwei Yang, Jun Jiang
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with biologic behavior with frequent distant metastasis. FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in a variety of biological processes as a tumor suppressor; however, the role of FAT4 in TNBC is still unclear. The aim of our study was to identify the role of FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a series of TNBC tissues...
November 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27811364/erbb2-mutation-is-associated-with-a-worse-prognosis-in-patients-with-cdh1-altered-invasive-lobular-cancer-of-the-breast
#9
Zheng Ping, Gene P Siegal, Shuko Harada, Isam-Eldin Eltoum, Mariam Youssef, Tiansheng Shen, Jianbo He, Yingjie Huang, Dongquan Chen, Yiping Li, Kirby I Bland, Helena R Chang, Dejun Shen
E-cadherin (CDH1) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30-60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27696226/fat4-hypermethylation-and-grade-dependent-downregulation-in-gastric-adenocarcinoma
#10
Maryam Pilehchian Langroudi, Novin Nikbakhsh, Ali Akbar Samadani, Sadegh Fattahi, Hassan Taheri, Shahryar Shafaei, Galia Amirbozorgi, Reza Pilehchian Langroudi, Haleh Akhavan-Niaki
Gastric cancer is one of the major causes of death due to cancer in the world. It is a multi-factorial disease with epigenetic factors being also involved in its development. FAT4 is a tumor suppressor gene exerting an important role in cell adhesion. This study aimed at analyzing FAT4 expression and promoter methylation in gastric cancer. FAT4 expression was studied in 30 tumoral tissues and their non-tumoral counterparts using Taqman real time PCR method. Promoter methylation was assessed using bisulfite conversion method followed by sequencing...
March 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27381226/fat4-dchs1-signalling-controls-cell-proliferation-in-developing-vertebrae
#11
Anna Kuta, Yaopan Mao, Tina Martin, Catia Ferreira de Sousa, Danielle Whiting, Sana Zakaria, Ivan Crespo-Enriquez, Philippa Evans, Bartosz Balczerski, Baljinder Mankoo, Kenneth D Irvine, Philippa H Francis-West
The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between Drosophila and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear...
July 1, 2016: Development
https://www.readbyqxmd.com/read/27145737/dchs1-fat4-regulation-of-polarized-cell-behaviours-during-skeletal-morphogenesis
#12
Yaopan Mao, Anna Kuta, Ivan Crespo-Enriquez, Danielle Whiting, Tina Martin, Joanna Mulvaney, Kenneth D Irvine, Philippa Francis-West
Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown. An example of extreme diversity in the shape of a skeletal structure can be seen in the sternum, which varies considerably across species. Here we show that the Dchs1-Fat4 planar cell polarity pathway controls cell orientation in the early skeletal condensation to define the shape and relative dimensions of the mouse sternum. These changes fit a model of cell intercalation along differential Dchs1-Fat4 activity that drives a simultaneous narrowing, thickening and elongation of the sternum...
May 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27023521/knock-down-of-endogenous-bornavirus-like-nucleoprotein-1-inhibits-cell-growth-and-induces-apoptosis-in-human-oligodendroglia-cells
#13
Peng He, Lin Sun, Dan Zhu, Hong Zhang, Liang Zhang, Yujie Guo, Siwen Liu, Jingjing Zhou, Xiaoyan Xu, Peng Xie
Endogenous bornavirus-like nucleoprotein elements (EBLNs) have been discovered in the genomes of various animals including humans, whose functions have been seldom studied. To explore the biological functions of human EBLNs, we constructed a lentiviral vector expressing a short-hairpin RNA against human EBLN1, which successfully inhibited EBLN1 expression by above 80% in infected human oligodendroglia cells (OL cells). We found that EBLN1 silencing suppressed cell proliferation, induced G2/M phase arrest, and promoted apoptosis in OL cells...
March 24, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26792292/epigenetic-inactivation-of-fat4-contributes-to-gastric-field-cancerization
#14
COMPARATIVE STUDY
Satoshi Yoshida, Satoshi Yamashita, Tohru Niwa, Akiko Mori, Seiji Ito, Masao Ichinose, Toshikazu Ushijima
BACKGROUND: Gastric cancer (GC) is highly influenced by aberrant methylation, and accumulation of aberrant methylation in gastric mucosae produces an epigenetic field for cancerization. Nevertheless, the individual driver genes involved in such field cancerization are still unclear. Here, we aimed to demonstrate that FAT4, a novel tumor suppressor identified by exome sequencing of GC, is methylation-silenced and that such methylation is involved in epigenetic field cancerization for GC...
January 2017: Gastric Cancer
https://www.readbyqxmd.com/read/26773734/frequent-bcor-aberrations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#15
Akito Dobashi, Naoko Tsuyama, Reimi Asaka, Yuki Togashi, Kyoko Ueda, Seiji Sakata, Satoko Baba, Kana Sakamoto, Kiyohiko Hatake, Kengo Takeuchi
Extranodal natural killer/T cell lymphoma (ENKTL) is a rare subtype of lymphoma. Recurrent mutations in the JAK-STAT pathway, recently reported in ENKTL cases, are interesting in terms of both pathogenesis and inhibitor therapy. However, the frequencies of these mutations are low and variable among reports, and other pathognomonic mutations in ENKTL remain to be elucidated. In the present study, targeted capture sequencing of 602 cancer-related genes from 25 frozen ENKTL samples was performed, 11 of which were matched to normal samples...
May 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/26672766/inferring-the-progression-of-multifocal-liver-cancer-from-spatial-and-temporal-genomic-heterogeneity
#16
Jie-Yi Shi, Qingfeng Xing, Meng Duan, Zhi-Chao Wang, Liu-Xiao Yang, Ying-Jun Zhao, Xiao-Ying Wang, Yun Liu, Minghua Deng, Zhen-Bin Ding, Ai-Wu Ke, Jian Zhou, Jia Fan, Ya Cao, Jiping Wang, Ruibin Xi, Qiang Gao
Multifocal tumors developed either as independent tumors or as intrahepatic metastases, are very common in primary liver cancer. However, their molecular pathogenesis remains elusive. Herein, a patient with synchronous two hepatocellular carcinoma (HCC, designated as HCC-A and HCC-B) and one intrahepatic cholangiocarcinoma (ICC), as well as two postoperative recurrent tumors, was enrolled. Multiregional whole-exome sequencing was applied to these tumors to delineate the clonality and heterogeneity. The three primary tumors showed almost no overlaps in mutations and copy number variations...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26648538/age-related-mutations-and-chronic-myelomonocytic-leukemia
#17
COMPARATIVE STUDY
C C Mason, J S Khorashad, S K Tantravahi, T W Kelley, M S Zabriskie, D Yan, A D Pomicter, K R Reynolds, A M Eiring, Z Kronenberg, R L Sherman, J W Tyner, B K Dalley, K-H Dao, M Yandell, B J Druker, J Gotlib, T O'Hare, M W Deininger
Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy nearly confined to the elderly. Previous studies to determine incidence and prognostic significance of somatic mutations in CMML have relied on candidate gene sequencing, although an unbiased mutational search has not been conducted. As many of the genes commonly mutated in CMML were recently associated with age-related clonal hematopoiesis (ARCH) and aged hematopoiesis is characterized by a myelomonocytic differentiation bias, we hypothesized that CMML and aged hematopoiesis may be closely related...
April 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26633557/fat4-functions-as-a-tumour-suppressor-in-gastric-cancer-by-modulating-wnt-%C3%AE-catenin-signalling
#18
Jian Cai, Dan Feng, Liang Hu, Haiyang Chen, Guangzhen Yang, Qingping Cai, Chunfang Gao, Dong Wei
BACKGROUND: FAT4, a cadherin-related protein, was shown to function as a tumour suppressor; however, its role in human gastric cancer remains largely unknown. Here, we investigated the role of FAT4 in gastric cancer and examined the underlying molecular mechanisms. METHODS: The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of gastric cancer patients. The effects of FAT4 silencing on cell proliferation, migration, and invasion were assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay, and migration and invasion assays in gastric cancer cell lines in vitro and in a mouse xenograft model in vivo...
December 22, 2015: British Journal of Cancer
https://www.readbyqxmd.com/read/26575609/fat4-suppression-induces-yap-translocation-accounting-for-the-promoted-proliferation-and-migration-of-gastric-cancer-cells
#19
Liangang Ma, Jianxin Cui, Hongqing Xi, Shibo Bian, Bo Wei, Lin Chen
Fat4 functions as a Hippo signaling regulator which is involved in mammalian tissue development, differentiation and tumorigenesis. Loss of Fat4 due to frequent gene mutation was detected in a variety of tumors including gastric cancer, where Fat4 was recognized as a tumor suppressor, repressing cancer cell proliferation and adhesion. However, the detailed mechanisms linking Fat4 to its diverse functions and clinicopathological characteristics in gastric cancer remain unclear. Here, we silenced Fat4 using Fat4-shRNA in gastric cancer cells and found that this suppression led to the increase in phosphorylated Yap and nuclear accumulation of Yap, which associated to the promoted proliferation, migration and cell cycle progression...
2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/26511275/sall1-in-renal-stromal-progenitors-non-cell-autonomously-restricts-the-excessive-expansion-of-nephron-progenitors
#20
Tomoko Ohmori, Shunsuke Tanigawa, Yusuke Kaku, Sayoko Fujimura, Ryuichi Nishinakamura
The mammalian kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud, the former of which contains nephron progenitors. The third lineage, the stroma, fills up the interstitial space and is derived from distinct progenitors that express the transcription factor Foxd1. We showed previously that deletion of the nuclear factor Sall1 in nephron progenitors leads to their depletion in mice. However, Sall1 is expressed not only in nephron progenitors but also in stromal progenitors...
2015: Scientific Reports
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