Role of RUNX2 in Breast Carcinogenesis
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Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
RNA-Seq Transcriptome Analysis Of
on: Sequ ati en er c Le Luyer et al, Next Generat Sequenc & Applic 2015, 2:1 n in e g G & t x A DOI: 10.4172/2469-9853.1000112 e p Journal of p N l f i c o a l t a i o n r ISSN: 2469-9853n u s o J Next Generation Sequencing & Applications Research Article Open Access RNA-Seq Transcriptome Analysis of Pronounced Biconcave Vertebrae: A Common Abnormality in Rainbow Trout (Oncorhynchus mykiss, Walbaum) Fed a Low-Phosphorus Diet Le Luyer J1, Deschamps MH1, Proulx E1, Poirier Stewart N1, Droit A2, Sire JY3, Robert C1 and Vandenberg GW1* 1Département of des sciences animales, Pavillon Paul-Comtois, Université Laval, Québec, QC, Canada G1V 0A6, Canada 2Department of Molecular Medicine, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC, G1V 4G2 Canada 3Institut de Biologie Paris-Seine, UMR 7138-Evolution Paris-Seine, Université Pierre et Marie Curie, Paris, France Abstract The prevalence of bone deformities, particularly linked with mineral deficiency, is an important issue for fish production. Juvenile triploid rainbow trout (Oncorhynchus mykiss) were fed a low-phosphorus (P) diet for 27 weeks (60 to 630 g body mass). At study termination, 24.9% of the fish fed the low-P diet displayed homogeneous biconcave vertebrae (deformed vertebrae phenotype), while 5.5% displayed normal vertebral phenotypes for the entire experiment. The aim of our study was to characterize the deformed phenotype and identify the putative genes involved in the appearance of P deficiency-induced deformities. Both P status and biomechanical measurements showed that deformed vertebrae were significantly less mineralized (55.0 ± 0.4 and 59.4 ± 0.5,% ash DM, for deformed and normal vertebrae, respectively) resulting in a lower stiffness (80.3 ± 9.0 and 140.2 ± 6.3 N/mm, for deformed and normal phenotypes, respectively). -
Jdp2 Downregulates Trp53 Transcription to Promote Leukaemogenesis in the Context of Trp53 Heterozygosity
Oncogene (2013) 32, 397 --402 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc SHORT COMMUNICATION Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity L van der Weyden1, AG Rust1,4, RE McIntyre1,4, CD Robles-Espinoza1, M del Castillo Velasco-Herrera1, R Strogantsev2, AC Ferguson-Smith2, S McCarthy1, TM Keane1, MJ Arends3 and DJ Adams1 We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity. Oncogene (2013) 32, 397--402; doi:10.1038/onc.2012.56; published online 27 February 2012 Keywords: p53; Jdp2; transposon; heterozygosity; lymphoma; mice INTRODUCTION targeted by transposon insertion events leading to upregulated Genetic alterations of TP53 are frequent events in tumourigenesis Jdp2 expression and a decrease in Trp53 expression levels. Further and promote genomic instability, impair apoptosis, and contribute we illustrate that Jdp2 regulates the Trp53 promoter via an atypical to aberrant self-renewal.1--4 The spectrum of mutations that occur AP-1 binding site. -
Dedifferentiation and Neuronal Repression Define Familial Alzheimer’S Disease Andrew B
bioRxiv preprint doi: https://doi.org/10.1101/531202; this version posted November 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International licenseCaldwell. et al. BIORXIV/2019/531202 Dedifferentiation and neuronal repression define Familial Alzheimer’s Disease Andrew B. Caldwell1, Qing Liu2, Gary P. Schroth3, Douglas R. Galasko2, Shauna H. Yuan2,8, Steven L. Wagner2,4, & Shankar Subramaniam1,5,6,7* Affiliations 1Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. 2Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA. 3Illumina, Inc., San Diego, CA, USA. 4VA San Diego Healthcare System, La Jolla, CA, USA. 5Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. 6Department of Nanoengineering, University of California, San Diego, La Jolla, CA, USA. 7Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA. 8Present Address: N. Bud Grossman Center for Memory Research and Care, Department of Neurology, University of Minnesota, Minneapolis, MN, USA; GRECC, Minneapolis VA Health Care System, Minneapolis, MN, USA. *Correspondence: Correspondence and requests for materials should be addressed to S.S. ([email protected]). Abstract Early-Onset Familial Alzheimer’s Disease (EOFAD) is a dominantly inherited neurodegenerative disorder elicited by over 300 mutations in the PSEN1, PSEN2, and APP genes1. Hallmark pathological changes and symptoms observed, namely the accumulation of misfolded Amyloid-β (Aβ) in plaques and Tau aggregates in neurofibrillary tangles associated with memory loss and cognitive decline, are understood to be temporally accelerated manifestations of the more common sporadic Late-Onset Alzheimer’s Disease. -
A Dissertation Entitled the Androgen Receptor
A Dissertation entitled The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit Submitted to the Graduate Faculty as partial fulfillment of the requirements for the PhD Degree in Biomedical science Dr. Manohar Ratnam, Committee Chair Dr. Lirim Shemshedini, Committee Member Dr. Robert Trumbly, Committee Member Dr. Edwin Sanchez, Committee Member Dr. Beata Lecka -Czernik, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo August 2011 Copyright 2011, Mesfin Gonit This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit As partial fulfillment of the requirements for the PhD Degree in Biomedical science The University of Toledo August 2011 Prostate cancer depends on the androgen receptor (AR) for growth and survival even in the absence of androgen. In the classical models of gene activation by AR, ligand activated AR signals through binding to the androgen response elements (AREs) in the target gene promoter/enhancer. In the present study the role of AREs in the androgen- independent transcriptional signaling was investigated using LP50 cells, derived from parental LNCaP cells through extended passage in vitro. LP50 cells reflected the signature gene overexpression profile of advanced clinical prostate tumors. The growth of LP50 cells was profoundly dependent on nuclear localized AR but was independent of androgen. Nevertheless, in these cells AR was unable to bind to AREs in the absence of androgen. -
Regulation of Runx2 Accumulation and Its Consequences
Regulation of Runx2 Accumulation and Its Consequences Junko Shimazu Submitted in partial fulfillment of the requirement for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2016 ©2016 Junko Shimazu All Rights Reserved ABSTRACT Regulation of Runx2 Accumulation and Its Consequences Junko Shimazu Osteoblasts are bone-forming cells and therefore they are responsible of the synthesis of type I collagen, the main component of bone matrix. However, there is an apparent disconnect between the regulation of osteoblast differentiation and bone formation since the synthesis of Type I collagen precedes the expression of Runx2, the earliest determinant of osteoblast differentiation. Recently, genetic experiments in the mouse have revealed the existence of an unexpected cross-regulation between bone and other organs. In particular this body of work has highlighted the importance of osteoblasts as endocrine cells to regulate whole-body glucose homeostasis by secretion of a hormone, osteocalcin. However, the fundamental question of why bone regulates glucose homeostasis remained to be answered. Therefore, in my thesis, considering that bone is a metabolically demanding organ that constantly renews itself, I hypothesized that characterizing the connection between the need of glucose as a main nutrient in osteoblasts and bone development will provide a key to deeper understanding of why bone regulates glucose homeostasis. My work shows here that glucose uptake through GLUT1 in osteoblasts is needed for osteoblast differentiation by suppressing the AMPK-dependent activation by phosphorylation at S148 of Smurf1 that targets Runx2 for degradation. I also uncovered the mechanism of action of Smurf1 in this setting. -
Effects of Estrogen Receptor and Wnt Signaling Activation On
International Journal of Molecular Sciences Article Effects of Estrogen Receptor and Wnt Signaling Activation on Mechanically Induced Bone Formation in a Mouse Model of Postmenopausal Bone Loss 1, , 1, 1 1 Astrid Liedert * y, Claudia Nemitz y, Melanie Haffner-Luntzer , Fabian Schick , Franz Jakob 2 and Anita Ignatius 1 1 Institute of Orhopedic Research and Biomechanics, Trauma Research Center Ulm, University Medical Center Ulm, 89081 Ulm, Germany; [email protected] (C.N.); melanie.haff[email protected] (M.H.-L.); [email protected] (F.S.); [email protected] (A.I.) 2 Orthopaedic Center for Musculoskeletal Research, University of Würzburg, 97074 Würzburg, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-731-500-55333; Fax: +49-731-500-55302 These authors contributed equally to the study. y Received: 14 September 2020; Accepted: 31 October 2020; Published: 5 November 2020 Abstract: In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. -
Genome-Wide Screen for Differentially Methylated Long Noncoding Rnas
OPEN Oncogene (2017) 36, 6446–6461 www.nature.com/onc ORIGINAL ARTICLE Genome-wide screen for differentially methylated long noncoding RNAs identifies Esrp2 and lncRNA Esrp2-as regulated by enhancer DNA methylation with prognostic relevance for human breast cancer K Heilmann, R Toth, C Bossmann, K Klimo, C Plass and C Gerhauser The majority of long noncoding RNAs (lncRNAs) is still poorly characterized with respect to function, interactions with protein- coding genes, and mechanisms that regulate their expression. As for protein-coding RNAs, epigenetic deregulation of lncRNA expression by alterations in DNA methylation might contribute to carcinogenesis. To provide genome-wide information on lncRNAs aberrantly methylated in breast cancer we profiled tumors of the C3(1) SV40TAg mouse model by MCIp-seq (Methylated CpG Immunoprecipitation followed by sequencing). This approach detected 69 lncRNAs differentially methylated between tumor tissue and normal mammary glands, with 26 located in antisense orientation of a protein-coding gene. One of the hypomethylated lncRNAs, 1810019D21Rik (now called Esrp2-antisense (as)) was identified in proximity to the epithelial splicing regulatory protein 2 (Esrp2) that is significantly elevated in C3(1) tumors. ESRPs were shown previously to have a dual role in carcinogenesis. Both gain and loss have been associated with poor prognosis in human cancers, but the mechanisms regulating expression are not known. In- depth analyses indicate that coordinate overexpression of Esrp2 and Esrp2-as inversely correlates with DNA methylation. Luciferase reporter gene assays support co-expression of Esrp2 and the major short Esrp2-as variant from a bidirectional promoter, and transcriptional regulation by methylation of a proximal enhancer. -
Twist1 Is a TNF-Inducible Inhibitor of Clock Mediated Activation of Period Genes
RESEARCH ARTICLE Twist1 Is a TNF-Inducible Inhibitor of Clock Mediated Activation of Period Genes Daniel Meier1, Martin Lopez1, Paul Franken2, Adriano Fontana1* 1 Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland, 2 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland * [email protected] Abstract Background Activation of the immune system affects the circadian clock. Tumor necrosis factor (TNF) and Interleukin (IL)-1β inhibit the expression of clock genes including Period (Per) genes and the PAR-bZip clock-controlled gene D-site albumin promoter-binding protein (Dbp). These effects are due to cytokine-induced interference of E-box mediated transcription of OPEN ACCESS clock genes. In the present study we have assessed the two E-box binding transcriptional Citation: Meier D, Lopez M, Franken P, Fontana A regulators Twist1 and Twist2 for their role in cytokine induced inhibition of clock genes. (2015) Twist1 Is a TNF-Inducible Inhibitor of Clock Mediated Activation of Period Genes. PLoS ONE 10 (9): e0137229. doi:10.1371/journal.pone.0137229 Methods Editor: Henrik Oster, University of Lübeck, The expression of the clock genes Per1, Per2, Per3 and of Dbp was assessed in NIH-3T3 GERMANY mouse fibroblasts and the mouse hippocampal neuronal cell line HT22. Cells were treated Received: June 17, 2015 for 4h with TNF and IL-1β. The functional role of Twist1 and Twist2 was assessed by siR- NAs against the Twist genes and by overexpression of TWIST proteins. In luciferase (luc) Accepted: August 14, 2015 assays NIH-3T3 cells were transfected with reporter gene constructs, which contain a Published: September 11, 2015 3xPer1 E-box or a Dbp E-box. -
Supplementary Information
Osa et al Supplementary Information Clinical implications of monitoring nivolumab immunokinetics in previously treated non– small cell lung cancer patients Akio Osa, Takeshi Uenami, Shohei Koyama, Kosuke Fujimoto, Daisuke Okuzaki, Takayuki Takimoto, Haruhiko Hirata, Yukihiro Yano, Soichiro Yokota, Yuhei Kinehara, Yujiro Naito, Tomoyuki Otsuka, Masaki Kanazu, Muneyoshi Kuroyama, Masanari Hamaguchi, Taro Koba, Yu Futami, Mikako Ishijima, Yasuhiko Suga, Yuki Akazawa, Hirotomo Machiyama, Kota Iwahori, Hyota Takamatsu, Izumi Nagatomo, Yoshito Takeda, Hiroshi Kida, Esra A. Akbay, Peter S. Hammerman, Kwok-kin Wong, Glenn Dranoff, Masahide Mori, Takashi Kijima, Atsushi Kumanogoh Supplemental Figures 1 – 8 1 Osa et al Supplemental Figure 1. The frequency of nivolumab-bound T cells was maintained in patients who continued treatment. Nivolumab binding in CD8 and CD4 T cells was analyzed at two follow-up points, as indicated, in fresh peripheral blood from three representative cases from protocol 1 that continued treatment. 2 Osa et al Supplemental Figure 2. Long-term follow-up of nivolumab binding to T cells from fresh whole blood. Nivolumab binding was followed up in fresh peripheral blood from an additional case, Pt.7. 3 Osa et al Supplemental Figure 3. Long-term duration of nivolumab binding is due to sustained circulation of residual nivolumab in plasma. (A) PBMCs acquired from Pt.8 and 9 at pretreatment (pre PBMCs) and after a single dose (post 1 PBMCs) were cultured in regular medium without nivolumab (top and middle). Pre PBMCs were also incubated with 10 µg/ml nivolumab in vitro before the cultures were started (bottom). Nivolumab binding status was monitored at the indicated time points. -
RUNX2 Regulates Leukemic Cell Metabolism and Chemotaxis in High-Risk T Cell Acute Lymphoblastic Leukemia
RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia Filip Matthijssens, … , Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska J Clin Invest. 2021;131(6):e141566. https://doi.org/10.1172/JCI141566. Research Article Oncology Graphical abstract Find the latest version: https://jci.me/141566/pdf The Journal of Clinical Investigation RESEARCH ARTICLE RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia Filip Matthijssens,1,2 Nitesh D. Sharma,3,4 Monique Nysus,3,4 Christian K. Nickl,3,4 Huining Kang,4,5 Dominique R. Perez,4,6 Beatrice Lintermans,1,2 Wouter Van Loocke,1,2 Juliette Roels,1,2 Sofie Peirs,1,2 Lisa Demoen,1,2 Tim Pieters,1,2 Lindy Reunes,1,2 Tim Lammens,2,7 Barbara De Moerloose,2,7 Filip Van Nieuwerburgh,8 Dieter L. Deforce,8 Laurence C. Cheung,9,10 Rishi S. Kotecha,9,10 Martijn D.P. Risseeuw,2,11 Serge Van Calenbergh,2,11 Takeshi Takarada,12 Yukio Yoneda,13 Frederik W. van Delft,14 Richard B. Lock,15 Seth D. Merkley,5 Alexandre Chigaev,4,6 Larry A. Sklar,4,6 Charles G. Mullighan,16 Mignon L. Loh,17 Stuart S. Winter,18 Stephen P. Hunger,19 Steven Goossens,1,2,20 Eliseo F. Castillo,5 Wojciech Ornatowski,21 Pieter Van Vlierberghe,1,2 and Ksenia Matlawska-Wasowska3,4 1Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. 2Cancer Research Institute Ghent (CRIG), Ghent, Belgium. 3Department of Pediatrics, Division of Hematology-Oncology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.