DOCSLIB.ORG

Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease 6418 Vol. 10, 6418–6431, October 1, 2004 Clinical Cancer Research Featured Article Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease Olga Modlich,1 Hans-Bernd Prisack,1 determined by a different platform was not always satis- Marc Munnes,2 Werner Audretsch,3 and fying. Hans Bojar1 Conclusions: This study has demonstrated the potential 1 of monitoring posttreatment changes in gene expression as a Institute of Chemical Oncology, University of Du¨sseldorf, measure of the pharmacodynamics of drugs. As a clinical Du¨sseldorf; 2Bayer Healthcare AG, Diagnostic Research Germany, Leverkusen; and 3Interdisciplinary Breast Center IBC, City Hospital laboratory model, it can be useful to identify patients with Du¨sseldorf, Du¨sseldorf, Germany sensitive and reactive tumors and to help for optimized choice for sequential therapy and obviously improve relapse- free and overall survival. ABSTRACT Purpose: Our goal was to identify genes undergoing expressional changes shortly after the beginning of neoad- INTRODUCTION juvant chemotherapy for primary breast cancer. Breast cancer, clinically, is a very heterogeneous disease. Experimental Design: The biopsies were taken from The clinical heterogeneity of breast cancers is due to a broad patients with primary breast cancer prior to any treatment diversity of somatic mutations and epigenetic rearrangements and 24 hours after the beginning of the neoadjuvant chem- changing the expression of many genes. Although much effort otherapy. Expression analyses from matched pair samples has been made to develop an optimal clinical treatment course representing 25 patients were carried out with Clontech for an individual patient with breast cancer, only little progress filter arrays. A subcohort of those 25 paired samples were could be achieved predicting the individual’s response to a additionally analyzed with the Affymetrix GeneChip plat- certain therapy. Such predictions are usually based on standard form. All of the transcripts from both platforms were que- clinical conditions such as tumor stage and grade, estrogen ried for expressional changes. receptor (ER) and progesterone receptor (PgR) status, growth Results: Performing hierarchical cluster analysis, we rate, overexpression of the HER2/neu and p53 oncogenes (1). clustered pre- and posttreatment samples from individual However, evidence about association of ER and/or PgR gene patients more closely to each other than the samples taken expression with outcome prediction for adjuvant endocrine from different patients. This reflects the rather low number chemotherapy are still controversial. Studies have shown that of transcripts responding directly to the drugs used. Al- levels of ER and PgR gene expression in breast cancer patients though transcriptional drug response occurring during ther- are of prognostic importance independently from a subsequent apy differed between individual patients, two genes adjuvant chemotherapy (2–4). Oppositely, a newer study has (p21WAF1/CIP1 and MIC-1) were up-regulated in posttreat- demonstrated that PgR status is an independent predictive factor ment samples. This could be validated by semiquantitative that improves outcome prediction for adjuvant endocrine ther- and real-time reverse transcription-PCR. Partial least- apy (5). Moreover, elevated ER and PgR levels are known to be discriminant analysis based on approximately 25 genes in- significantly associated with a progressively better response to dependently identified by either Clontech or Affymetrix tamoxifen and longer survival in ER(ϩ) metastatic breast cancer platforms could clearly discriminate pre- and posttreatment (6). From the theoretical point of view, it is unexpected that the samples. However, correlation of certain gene expression therapeutic response in patients with breast cancer might be levels as well as of differential patterns and clusters as independent from the ER/PgR status. It is more probable that the prognostic impact of receptors’ expression depends on the im- pact of other variables, e.g., the impact of the ERBB2 receptor (7, 8). When conventional biological techniques are used, find- Received 5/26/04; revised 6/24/04; accepted 6/28/04. ing such factors is problematical because all of these techniques The costs of publication of this article were defrayed in part by the survey one gene at a time. payment of page charges. This article must therefore be hereby marked For a few years, DNA microarray technology has been very advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. useful for quantitative measurements of expression levels of Note: Supplementary data for this article can be found at Clinical thousands of genes simultaneously in one sample. Thus far, this Cancer Research Online (http://clincancerres.aacrjournals.org). technology has been used for the classification of cancer tissues, Requests for reprints: Olga Modlich, Institut fu¨r Onkologische Che- e.g., breast tumors (9–24), prediction of metastasis and patient’s mie, Heinrich Heine Universita¨t Du¨sseldorf, Moorenstr. 5, D-40225 Du¨sseldorf, Germany. Phone: 49-211-811-4302; Fax: 49-211-811-5114; outcome (25–38), and tumor response to chemotherapy (39–43). E-mail: [email protected]. It is a well-established fact that adjuvant systematic ©2004 American Association for Cancer Research. treatment after surgery reduces the risk of disease relapse and Downloaded from clincancerres.aacrjournals.org on September 29, 2021. © 2004 American Association for Cancer Research. Clinical Cancer Research 6419 death in patients with primary operable breast cancer (44). As MATERIALS AND METHODS an alternative therapeutic concept, neoadjuvant or primary Patients and Clinical Specimens. From September 1999 systemic therapy (PST) can be offered either to those patients to June 2001, patients with primary breast cancer were enrolled with larger inoperable breast cancers or to patients interested with informed consent for this study with neoadjuvant EC or ET in breast-conserving surgery (45–53). The PST in general do treatment (epirubicin, 90 mg/m2, and cyclophosphamide, 600 mg/ not offer a survival advantage over standard adjuvant treat- m2, or Taxol, 175 mg/m2) as the first therapeutic intervention prior ment, but may identify patients with a pathologically con- to surgery (Table 1). Tumor samples were taken according to firmed complete response (45, 46). This clinical response to institutional review board guidelines. Serial core biopsies of the PST is associated with improved survival (50, 54, 55) and primary tumor were performed before treatment and 24 hours after reflects a great benefit to ϳ14% of the PST-treated patients. the initiation of the first course of the chemotherapy from a locally Studies elaborating PST have demonstrated that early gene anesthetized region with Bard MAGNUM Biopsy Instrument (C.R. expression changes are significantly associated with clinical Bard, Inc., Covington, GA) with Bard Magnum biopsy needles response (56, 57). (BIP GmbH, Tuerkenfeld, Germany). Serial biopsies were taken from a distinct area of the tumor with a 90-degree angle and an In general, all patients of a given cohort do receive the additional skin entry site. This approach was used to avoid the same treatment, even though many will fail in treatment success. detection of gene expression unrelated to treatment, such as tissue Biomarkers reflecting the tumor response can function as sen- injury-related processes. All biopsy samples were snap-frozen in sitive short-term surrogates of long-term outcome. The use of liquid nitrogen and stored at Ϫ80°C until further processing. He- such biomarkers will make chemotherapy more effective for the matoxylin and eosin-stained sections from tumor specimens were individual patient and will allow the changing of regimens early, examined to assess the relative amounts of tumor cells, benign in case of nonresponding tumors as far as the level of evidence epithelium, stroma, and lymphocytes. Standard clinical factors such for biomarker studies is obtained. as ER, PgR, Ki-67, p53, cerbB2/HER2neu have been routinely With this study, we aimed to identify effects of epirubicin/ defined4 in our laboratory. cyclophosphamide (EC) or epirubicin/taxol (ET) treatment on Total RNA Isolation, cDNA Probe Synthesis, and Atlas gene expression in primary breast cancers at 24 hours after the Array Data Analysis. Total RNA from tissue specimens was first treatment. Cyclophosphamide and epirubicin are common extracted according to the protocol recommended for the Atlas therapeutics for advanced and metastatic breast cancer (58). Pure Total RNA labeling system (BD Biosciences Clontech). The Moreover, a therapeutic advantage of epirubicin is the higher amount and quality of RNA were evaluated with UV spectropho- cumulative dose at which the anthracycline-induced cardiotox- tometry (Photometer ECOM 6122, Eppendorf AG, Hamburg, Ger- icity becomes clinically evident in contrast to the more fre- many), agarose gel electrophoresis, and Agilent 2100 Bioanalyzer quently used doxorubicin (Adriamycin). On the other hand, RNA 6000 LabChip kit (Agilent Technologies GmbH, Boeblingen, 32 taxanes have quickly been established as important chemother- Germany) following the manufacturer’s instructions. ␣ P-labeled apeutic agents in the armamentarium of drugs to treat breast cDNA probes were prepared from 5–10 ␮g of total RNA with cancer (59). Expression profiles of
Load more

Recommended publications
  • Role of Cyclosporine in Gingival Hyperplasia: an in Vitro Study on Gingival Fibroblasts
    International Journal of Molecular Sciences Article Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts 1, , 2, 3 3 Dorina Lauritano * y , Annalisa Palmieri y, Alberta Lucchese , Dario Di Stasio , Giulia Moreo 1 and Francesco Carinci 4 1 Department of Medicine and Surgery, Centre of Neuroscience of Milan, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, via Belmoro 8, 40126 Bologna, Italy; [email protected] 3 Multidisciplinary Department of Medical and Dental Specialties, University of Campania-Luigi Vanvitelli, 80138 Naples, Italy; [email protected] (A.L.); [email protected] (D.D.S.) 4 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-335-679-0163 These authors contributed equally to this work. y Received: 25 November 2019; Accepted: 13 January 2020; Published: 16 January 2020 Abstract: Background: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. Materials and methods: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control.
    [Show full text]
  • Lectin-Affinity Chromatography Brain Glycoproteomics and Alzheimer
    50 DOI 10.1002/prca.201000070 Proteomics Clin. Appl. 2011, 5, 50–56 REVIEW Lectin-affinity chromatography brain glycoproteomics and Alzheimer disease: Insights into protein alterations consistent with the pathology and progression of this dementing disorder D. Allan Butterfield and Joshua B. Owen Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington KY, USA Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the Received: July 7, 2010 accumulation of senile plaques and neurofibrillary tangles, and both these pathological Revised: August 4, 2010 hallmarks of AD are extensively modified by glycosylation. Mounting evidence shows that Accepted: August 10, 2010 alterations in glycosylation patterns influence the pathogenesis and progression of AD, but the vast number of glycan motifs and potential glycosylation sites of glycoproteins has made the field of glycobiology difficult. However, the advent of glycoproteomics has produced major strides in glycoprotein identification and glycosylation site mapping. The use of lectins, proteins that have strong affinity for specific carbohydrate epitopes, to enrich glycoprotein fractions coupled with modern MS, have yielded techniques to elucidate the glycoproteome in AD. Proteomic studies have identified brain proteins in AD and arguably the earliest form of AD, mild cognitive impairment, with altered affinity for Concanavalin-A and wheat germ agglutinin lectins that are consistent with the pathology and progression of this disorder. This is a relatively nascent field of proteomics research in brain, so future studies of lectin-based brain protein separations may lead to additional insights into AD pathogenesis and progression. Keywords: Alzheimers disease (AD) / Lectin-chromatography / Mild cognitive impairment (MCI) / MS / Synaptic alterations 1 Introduction ized pathologically by the accumulation of senile plaques (SPs) and neurofibrillary tangles (NFTs).
    [Show full text]
  • Targeted Genes and Methodology Details for Neuromuscular Genetic Panels
    Targeted Genes and Methodology Details for Neuromuscular Genetic Panels Reference transcripts based on build GRCh37 (hg19) interrogated by Neuromuscular Genetic Panels Next-generation sequencing (NGS) and/or Sanger sequencing is performed Motor Neuron Disease Panel to test for the presence of a mutation in these genes. Gene GenBank Accession Number Regions of homology, high GC-rich content, and repetitive sequences may ALS2 NM_020919 not provide accurate sequence. Therefore, all reported alterations detected ANG NM_001145 by NGS are confirmed by an independent reference method based on laboratory developed criteria. However, this does not rule out the possibility CHMP2B NM_014043 of a false-negative result in these regions. ERBB4 NM_005235 Sanger sequencing is used to confirm alterations detected by NGS when FIG4 NM_014845 appropriate.(Unpublished Mayo method) FUS NM_004960 HNRNPA1 NM_031157 OPTN NM_021980 PFN1 NM_005022 SETX NM_015046 SIGMAR1 NM_005866 SOD1 NM_000454 SQSTM1 NM_003900 TARDBP NM_007375 UBQLN2 NM_013444 VAPB NM_004738 VCP NM_007126 ©2018 Mayo Foundation for Medical Education and Research Page 1 of 14 MC4091-83rev1018 Muscular Dystrophy Panel Muscular Dystrophy Panel Gene GenBank Accession Number Gene GenBank Accession Number ACTA1 NM_001100 LMNA NM_170707 ANO5 NM_213599 LPIN1 NM_145693 B3GALNT2 NM_152490 MATR3 NM_199189 B4GAT1 NM_006876 MYH2 NM_017534 BAG3 NM_004281 MYH7 NM_000257 BIN1 NM_139343 MYOT NM_006790 BVES NM_007073 NEB NM_004543 CAPN3 NM_000070 PLEC NM_000445 CAV3 NM_033337 POMGNT1 NM_017739 CAVIN1 NM_012232 POMGNT2
    [Show full text]
  • 2335 Roles of Molecules Involved in Epithelial/Mesenchymal Transition
    [Frontiers in Bioscience 13, 2335-2355, January 1, 2008] Roles of molecules involved in epithelial/mesenchymal transition during angiogenesis Giulio Ghersi Dipartimento di Biologia Cellulare e dello Sviluppo, Universita di Palermo, Italy TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Extracellular matrix 3.1. ECM and integrins 3.2. Basal lamina components 4. Cadherins. 4.1. Cadherins in angiogenesis 5. Integrins. 5.1. Integrins in angiogenesis 6. Focal adhesion molecules 7. Proteolytic enzymes 7.1. Proteolytic enzymes inhibitors 7.2. Proteolytic enzymes in angiogenesis 8. Perspective 9. Acknowledgements 10. References 1.ABSTRACT 2. INTRODUCTION Formation of vessels requires “epithelial- Growth of new blood vessels (angiogenesis) mesenchymal” transition of endothelial cells, with several plays a key role in several physiological processes, such modifications at the level of endothelial cell plasma as vascular remodeling during embryogenesis and membranes. These processes are associated with wound healing tissue repair in the adult; as well as redistribution of cell-cell and cell-substrate adhesion pathological processes, including rheumatoid arthritis, molecules, cross talk between external ECM and internal diabetic retinopathy, psoriasis, hemangiomas, and cytoskeleton through focal adhesion molecules and the cancer (1). Vessel formation entails the “epithelial- expression of several proteolytic enzymes, including matrix mesenchymal” transition of endothelial cells (ECs) “in metalloproteases and serine proteases. These enzymes with vivo”; a similar phenotypic exchange can be induced “in their degradative action on ECM components, generate vitro” by growing ECs to low cell density, or in “wound molecules acting as activators and/or inhibitors of healing” experiments or perturbing cell adhesion and angiogenesis. The purpose of this review is to provide an associated molecule functions.
    [Show full text]
  • Effect of Nanoparticles on the Expression and Activity of Matrix Metalloproteinases
    Nanotechnol Rev 2018; 7(6): 541–553 Review Magdalena Matysiak-Kucharek*, Magdalena Czajka, Krzysztof Sawicki, Marcin Kruszewski and Lucyna Kapka-Skrzypczak Effect of nanoparticles on the expression and activity of matrix metalloproteinases https://doi.org/10.1515/ntrev-2018-0110 Received September 14, 2018; accepted October 11, 2018; previously 1 Introduction published online November 15, 2018 Matrix metallopeptidases, commonly known as matrix Abstract: Matrix metallopeptidases, commonly known metalloproteinases (MMPs), are zinc-dependent proteo- as matrix metalloproteinases (MMPs), are a group of pro- lytic enzymes whose primary function is the degradation teolytic enzymes whose main function is the remodeling and remodeling of extracellular matrix (ECM) compo- of the extracellular matrix. Changes in the activity of nents. ECM is a complex, dynamic structure that condi- these enzymes are observed in many pathological states, tions the proper tissue architecture. MMPs by digesting including cancer metastases. An increasing body of evi- ECM proteins eliminate structural barriers and allow dence indicates that nanoparticles (NPs) can lead to the cell migration. Moreover, by hydrolyzing extracellularly deregulation of MMP expression and/or activity both in released proteins, MMPs can change the activity of many vitro and in vivo. In this work, we summarized the current signal peptides, such as growth factors, cytokines, and state of knowledge on the impact of NPs on MMPs. The chemokines. MMPs are involved in many physiological literature analysis showed that the impact of NPs on MMP processes, such as embryogenesis, reproduction cycle, or expression and/or activity is inconclusive. NPs exhibit wound healing; however, their increased activity is also both stimulating and inhibitory effects, which might be associated with a number of pathological conditions, such dependent on multiple factors, such as NP size and coat- as diabetes, cardiovascular diseases and neurodegenera- ing or a cellular model used in the research.
    [Show full text]
  • Single-Cell Analysis Uncovers Fibroblast Heterogeneity
    ARTICLE https://doi.org/10.1038/s41467-020-17740-1 OPEN Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination ✉ Lars Muhl 1,2 , Guillem Genové 1,2, Stefanos Leptidis 1,2, Jianping Liu 1,2, Liqun He3,4, Giuseppe Mocci1,2, Ying Sun4, Sonja Gustafsson1,2, Byambajav Buyandelger1,2, Indira V. Chivukula1,2, Åsa Segerstolpe1,2,5, Elisabeth Raschperger1,2, Emil M. Hansson1,2, Johan L. M. Björkegren 1,2,6, Xiao-Rong Peng7, ✉ Michael Vanlandewijck1,2,4, Urban Lendahl1,8 & Christer Betsholtz 1,2,4 1234567890():,; Many important cell types in adult vertebrates have a mesenchymal origin, including fibro- blasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes. 1 Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre, Blickagången 6, SE-14157 Huddinge, Sweden.
    [Show full text]
  • In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
    applied sciences Article Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts Dorina Lauritano 1,*,† , Giulia Moreo 1,†, Fedora Della Vella 2 , Annalisa Palmieri 3, Francesco Carinci 4 and Massimo Petruzzi 2 1 Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy; [email protected] (F.D.V.); [email protected] (M.P.) 3 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmoro 8, 40126 Bologna, Italy; [email protected] 4 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected] † These authors contribute equally to this work. Abstract: Background: It has been proven that the antihypertensive agent nifedipine can cause gingi- val overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible patho- genetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed Citation: Lauritano, D.; Moreo, G.; significant upregulation in treated cells with respect to the control group, and cell adhesion gene Vella, F.D.; Palmieri, A.; Carinci, F.; CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time Petruzzi, M.
    [Show full text]
  • Tropomyosin Isoform Tpm2.1 Regulates Collective and Amoeboid Cell Migration and Cell Aggregation in Breast Epithelial Cells
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 56), pp: 95192-95205 Research Paper Tropomyosin isoform Tpm2.1 regulates collective and amoeboid cell migration and cell aggregation in breast epithelial cells HyeRim Shin1, Dayoung Kim1 and David M. Helfman1 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea Correspondence to: David M. Helfman, email: [email protected] Keywords: collective cell migration, amoeboid migration, cell aggregation, AXL receptor tyrosine kinase, metastasis Received: November 17, 2016 Accepted: June 20, 2017 Published: July 12, 2017 Copyright: Shin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines. Downregulation of Tpm2.1 using siRNA or shRNA resulted in retardation of collective cell migration but increase in single cell migration and invasion.
    [Show full text]
  • Competing Endogenous RNA Network Analysis Reveals Pivotal Cernas in Bladder Urothelial Carcinoma
    808 Original Article Competing endogenous RNA network analysis reveals pivotal ceRNAs in bladder urothelial carcinoma Yangle Li, Xiongbing Zu, Xiheng Hu, Cheng Zhao, Miao Mo, Benyi Fan Department of Urology, Xiangya Hospital, Central South University, Changsha, China Contributions: (I) Conception and design: All authors; (II) Administrative support: B Fan; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Y Li, X Zu, X Hu; (V) Data analysis and interpretation: Y Li, X Zu, C Zhao, M Mo; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Benyi Fan. 87 Xiangya Road, Changsha 410008, China. Email: [email protected]. Background: Bladder urothelial cancer (BUC) has become one of the most frequently occurring malignant tumors worldwide and it is of great importance to explore the molecular pathogenesis of bladder cancer. Emerging evidence has demonstrated that dysregulation of noncoding RNAs is critically involved in the tumorigenesis and progression of BUC. Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression and therefore form a competing endogenous RNA (ceRNA) network. ceRNA networks have been proven to play vital roles during tumorigenesis and progression. Elements involved in the ceRNA network have also been identified as potential therapeutic targets and prognostic biomarkers in various tumors. Understanding the regulatory mechanisms and functional roles of the ceRNA system will help understand tumorigenesis, progression mechanisms of BUC and develop therapeutics against cancer. Methods: In this study, we utilized the TCGA database and analyzed the multilevel expression profile of BUC. ceRNA regulatory networks were constructed by integrating tumor progression and prognosis information.
    [Show full text]
  • Snapshot: Actin Regulators II Anosha D
    SnapShot: Actin Regulators II Anosha D. Siripala and Matthew D. Welch Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA Representative Proteins Protein Family H. sapiens D. melanogaster C. elegans A. thaliana S. cerevisiae Endocytosis and Exocytosis ABP1/drebrin mABP1, drebrin, drebrin- †Q95RN0 †Q9XUT0 Abp1 like EPS15 EPS15 Eps-15 EHS-1 †Q56WL2 Pan1 HIP1R HIP1R †Q8MQK1 †O62142 Sla2 Synapsin synapsin Ia, Ib, IIa, IIb, III Synapsin SNN-1 Plasma Membrane Association Anillin anillin Scraps ANI-1, 2, 3 Annexins annexin A1–11, 13 (actin Annexin B9-11 NEX-1–4 ANN1-8 binding: 1, 2, 6) ERM proteins ezrin, radixin, moesin DMoesin ERM-1 MARCKS MARCKS, MRP/ Akap200 MACMARCKS/F52 Merlin *merlin/NF2 Merlin NFM-1 Protein 4.1 4.1R, G, N, B Coracle Spectrin α-spectrin (1–2), β-spectrin α-spectrin, β-spectrin, β heavy- SPC-1 (α-spectrin), UNC-70 (1–4), β heavy-spectrin/ spectrin/Karst (β-spectrin), SMA-1 (β heavy- karst spectrin) Identifi ed Cellular Role: X Membrane traffi cking and phagocytosis Cell-Cell Junctions X Cytokinesis α-catenin α-catenin 1–3 α-catenin HMP-1 X Cell surface organization and dynamics X Cell adhesion Afadin afadin/AF6 Canoe AFD-1 X Multiple functions ZO-1 ZO-1, ZO-2, ZO-3 ZO-1/Polychaetoid †Q56VX4 X Other/unknown Cell-Extracellular Matrix Junctions †UNIPROT database accession number *Mutation linked to human disease Dystrophin/utrophin *dystrophin, utrophin/ Dystrophin DYS-1 DRP1, DRP2 LASP LASP-1, LASP-2, LIM- Lasp †P34416 nebulette Palladin palladin Parvin α-, β-, χ-parvin †Q9VWD0 PAT-6
    [Show full text]
  • Identification of the Fatty Acid Synthase Interaction Network Via Itraq-Based Proteomics Indicates the Potential Molecular Mecha
    Huang et al. Cancer Cell Int (2020) 20:332 https://doi.org/10.1186/s12935-020-01409-2 Cancer Cell International PRIMARY RESEARCH Open Access Identifcation of the fatty acid synthase interaction network via iTRAQ-based proteomics indicates the potential molecular mechanisms of liver cancer metastasis Juan Huang1, Yao Tang1, Xiaoqin Zou1, Yi Lu1, Sha She1, Wenyue Zhang1, Hong Ren1, Yixuan Yang1,2* and Huaidong Hu1,2* Abstract Background: Fatty acid synthase (FASN) is highly expressed in various types of cancer and has an important role in carcinogenesis and metastasis. To clarify the mechanisms of FASN in liver cancer invasion and metastasis, the FASN protein interaction network in liver cancer was identifed by targeted proteomic analysis. Methods: Wound healing and Transwell assays was performed to observe the efect of FASN during migration and invasion in liver cancer. Isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry were used to identify proteins interacting with FASN in HepG2 cells. Diferential expressed proteins were validated by co-immunoprecipitation, western blot analyses and confocal microscopy. Western blot and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) were performed to demonstrate the mechanism of FASN regulating metastasis. Results: FASN knockdown inhibited migration and invasion of HepG2 and SMMC7721 cells. A total of, 79 proteins interacting with FASN were identifed. Additionally, gene ontology term enrichment analysis indicated that the majority of biological regulation and cellular processes that the FASN-interacting proteins were associated with. Co- precipitation and co-localization of FASN with fascin actin-bundling protein 1 (FSCN1), signal-induced proliferation- associated 1 (SIPA1), spectrin β, non-erythrocytic 1 (SPTBN1) and CD59 were evaluated.
    [Show full text]
  • Extracellular Matrix Alterations in Metastatic Processes
    International Journal of Molecular Sciences Review Extracellular Matrix Alterations in Metastatic Processes Mayra Paolillo * and Sergio Schinelli Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; [email protected] * Correspondence: [email protected] Received: 17 September 2019; Accepted: 30 September 2019; Published: 7 October 2019 Abstract: The extracellular matrix (ECM) is a complex network of extracellular-secreted macromolecules, such as collagen, enzymes and glycoproteins, whose main functions deal with structural scaffolding and biochemical support of cells and tissues. ECM homeostasis is essential for organ development and functioning under physiological conditions, while its sustained modification or dysregulation can result in pathological conditions. During cancer progression, epithelial tumor cells may undergo epithelial-to-mesenchymal transition (EMT), a morphological and functional remodeling, that deeply alters tumor cell features, leading to loss of epithelial markers (i.e., E-cadherin), changes in cell polarity and intercellular junctions and increase of mesenchymal markers (i.e., N-cadherin, fibronectin and vimentin). This process enhances cancer cell detachment from the original tumor mass and invasiveness, which are necessary for metastasis onset, thus allowing cancer cells to enter the bloodstream or lymphatic flow and colonize distant sites. The mechanisms that lead to development of metastases in specific sites are still largely obscure but modifications occurring in target tissue ECM are being intensively studied. Matrix metalloproteases and several adhesion receptors, among which integrins play a key role, are involved in metastasis-linked ECM modifications. In addition, cells involved in the metastatic niche formation, like cancer associated fibroblasts (CAF) and tumor associated macrophages (TAM), have been found to play crucial roles in ECM alterations aimed at promoting cancer cells adhesion and growth.
    [Show full text]