Rho GTPases: functions and association with cancer

No abstract is available for this paper.

• Publication year

  2007

• Venue

  Clinical and Experimental Metastasis

• Publication date

  2007-11-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1007/s10585-007-9119-1PMID 18000759
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• RhoC is essential for the metastasis of gastric cancer

  2007cited by this paper
• Hyperactive Ras in developmental disorders and cancer

  2007cited by this paper
• ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion.

  2007cited by this paper
• GEF what? Dock180 and related proteins help Rac to polarize cells in new ways.

  2007cited by this paper
• GEFs and GAPs: critical elements in the control of small G proteins.

  2007cited by this paper
• Rho activation at a glance

  2007cited by this paper
• mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration

  2007cited by this paper
• Current knowledge of the large RhoGAP family of proteins

  2007cited by this paper
• α6β4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-κB-dependent resistance to apoptosis in 3D mammary acini

  2007cited by this paper
• alpha6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-kappaB-dependent resistance to apoptosis in 3D mammary acini.

  2007cited by this paper
• Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases.

  2007cited by this paper
• Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1

  2007cited by this paper
• The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity.

  2007cited by this paper
• The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization

  2007cited by this paper
• GTP‐binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo

  2007cited by this paper
• Overexpression of RhoE Has a Prognostic Value in Non–Small Cell Lung Cancer

  2007cited by this paper
• RhoC GTPase Expression as a Potential Marker of Lymph Node Metastasis in Squamous Cell Carcinomas of the Head and Neck

  2006cited by this paper
• D4-GDI, a Rho GTPase regulator, promotes breast cancer cell invasiveness.

  2006cited by this paper
• Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma

  2006cited by this paper
• Complex networks orchestrate epithelial–mesenchymal transitions

  2006influential reference
• Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking.

  2006cited by this paper
• The Rac Activator Tiam1 Is a Wnt-responsive Gene That Modifies Intestinal Tumor Development*

  2006influential reference
• Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells.

  2006cited by this paper
• The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms

  2006cited by this paper
• Interaction between Tiam1 and the Arp2/3 complex links activation of Rac to actin polymerization.

  2006cited by this paper
• The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking.

  2006influential reference
• The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-Src

  2006cited by this paper
• Cadherins in development: cell adhesion, sorting, and tissue morphogenesis.

  2006cited by this paper
• Prognostic relevance of Tiam1 protein expression in prostate carcinomas

  2006cited by this paper
• Stress fibers are generated by two distinct actin assembly mechanisms in motile cells

  2006cited by this paper
• Tiam1 takes PARt in cell polarity.

  2006cited by this paper
• p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho.

  2006cited by this paper
• Generation and Characterization of Rac3 Knockout Mice

  2005cited by this paper
• Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis.

  2005cited by this paper
• CZH proteins: a new family of Rho-GEFs

  2005cited by this paper
• Expression of Rac1b stimulates NF-kappaB-mediated cell survival and G1/S progression.

  2005influential reference
• Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability

  2005cited by this paper
• Rho GTPases: biochemistry and biology.

  2005influential reference
• RhoGDI: multiple functions in the regulation of Rho family GTPase activities.

  2005cited by this paper
• The Ras superfamily at a glance

  2005cited by this paper
• PAR-6–PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1

  2005cited by this paper
• The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex

  2005influential reference
• Cadherins and catenins in breast cancer.

  2005cited by this paper
• Generation of rac3 Null Mutant Mice: Role of Rac3 in Bcr/Abl-Caused Lymphoblastic Leukemia

  2005cited by this paper
• The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration

  2005cited by this paper
• GDIs: central regulatory molecules in Rho GTPase activation.

  2005cited by this paper
• Rho GTPases and the control of cell behaviour.

  2005cited by this paper
• Tiam1-IRSp53 Complex Formation Directs Specificity of Rac-Mediated Actin Cytoskeleton Regulation

  2005cited by this paper
• Signaling interplay in Ras superfamily function.

  2005cited by this paper
• Small G‐protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis

  2005cited by this paper
• RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis.

  2005cited by this paper
• Tiam1-IRSp53 Complex Formation Directs Specificity of Rac-Mediated Actin Cytoskeleton Regulation

  2005cited by this paper
• GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors

  2005cited by this paper
• The genetics of Pak

  2004cited by this paper
• ARHGAP8 is a novel member of the RHOGAP family related to ARHGAP1/CDC42GAP/p50RHOGAP: mutation and expression analyses in colorectal and breast cancers.

  2004cited by this paper
• Overexpression of RhoA, Rac1, and Cdc42 GTPases Is Associated with Progression in Testicular Cancer

  2004cited by this paper
• RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex.

  2004cited by this paper
• Functional Analysis of the Contribution of RhoA and RhoC GTPases to Invasive Breast Carcinoma

  2004cited by this paper
• Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma.

  2004cited by this paper
• Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation

  2004cited by this paper
• Expression of seven main Rho family members in gastric carcinoma.

  2004cited by this paper
• Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis.

  2004cited by this paper
• Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer

  2004cited by this paper
• Cdc42 - the centre of polarity

  2004cited by this paper
• Rho GTPases as Key Transducers of Proliferative Signals in G1 Cell Cycle Regulation

  2004cited by this paper
• Reduced Expression of Metastasis Suppressor RhoGDI2 Is Associated with Decreased Survival for Patients with Bladder Cancer

  2004cited by this paper
• The Rac Exchange Factor Tiam1 Is Required for the Establishment and Maintenance of Cadherin-based Adhesions*

  2004influential reference
• The Role of the Guanine Nucleotide Exchange Factor Tiam1 in Cellular Migration, Invasion, Adhesion and Tumor Progression

  2004cited by this paper
• Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass.

  2004cited by this paper
• Loss of RhoB Expression in Human Lung Cancer Progression

  2004cited by this paper
• Rho GTPases have diverse effects on the organization of the actin filament system.

  2004cited by this paper
• Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer.

  2003cited by this paper
• Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma.

  2003cited by this paper
• Redox-dependent downregulation of Rho by Rac

  2003cited by this paper
• Different regulation of the Trio Dbl‐Homology domains by their associated PH domains

  2003cited by this paper
• Tumor progression: Small GTPases and loss of cell-cell adhesion.

  2003cited by this paper
• Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma.

  2003cited by this paper
• DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

  2003cited by this paper
• The haematopoietic specific signal transducer Vav1 is expressed in a subset of human neuroblastomas

  2003cited by this paper
• Regulation of Tiam1–Rac signalling

  2003cited by this paper
• Calcium Signaling Regulates Translocation and Activation of Rac*

  2003cited by this paper
• Tuba, a Novel Protein Containing Bin/Amphiphysin/Rvs and Dbl Homology Domains, Links Dynamin to Regulation of the Actin Cytoskeleton*

  2003cited by this paper
• Cadherin Engagement Inhibits RhoA via p190RhoGAP*

  2003cited by this paper
• Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers.

  2003cited by this paper
• Atypical Rho GTPases Have Roles in Mitochondrial Homeostasis and Apoptosis*

  2003cited by this paper
• Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases

  2003cited by this paper
• Rho GTPase-activating proteins in cell regulation.

  2003cited by this paper
• Dissociation of GDP Dissociation Inhibitor and Membrane Translocation Are Required for Efficient Activation of Rac by the Dbl Homology-Pleckstrin Homology Region of Tiam*

  2003cited by this paper
• Actin dynamics control SRF activity by regulation of its coactivator MAL.

  2003cited by this paper
• Overexpression of betaPix-a in human breast cancer tissues.

  2003cited by this paper
• Control of vesicular trafficking by Rho GTPases.

  2003cited by this paper
• Overexpression of βPix-a in human breast cancer tissues

  2003cited by this paper
• Deleted in Liver Cancer (DLC) 2 Encodes a RhoGAP Protein with Growth Suppressor Function and Is Underexpressed in Hepatocellular Carcinoma*

  2003cited by this paper
• ROCKs: multifunctional kinases in cell behaviour

  2003cited by this paper
• Tumor-related Alternatively Spliced Rac1b Is Not Regulated by Rho-GDP Dissociation Inhibitors and Exhibits Selective Downstream Signaling*

  2003influential reference
• E-cadherin Homophilic Ligation Directly Signals through Rac and Phosphatidylinositol 3-Kinase to Regulate Adhesive Contacts*

  2002cited by this paper
• Rho GTPases in cell biology

  2002cited by this paper
• Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours

  2002influential reference
• Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.

  2002cited by this paper
• Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members.

  2002cited by this paper

• Multi-omics Characterization of Acquired Olaparib Resistance in BRCA1 and BRCA2 Mutant Breast Cancer Cell Lines

  2025cites this paper
• The Role of ROS and Its Sources in Tumorigenesis: Friend or Foe?

  2025cites this paper
• A GTPase activating protein Polrg1 regulates the development and cellulase expression of Penicillium oxalicum

  2025cites this paper
• Research progress of ECT2 and RhoA-related signaling pathways in gynecological tumors

  2025cites this paper
• A covalent inhibitor targeting Cys16 on RhoA in colorectal cancer.

  2025cites this paper
• A Rho-Type GTPase Protein Pocdc42 Regulates the Development and Cellulase Expression of Penicillium oxalicum

  2025cites this paper
• Hormonal control of the mammary blood-milk barrier and its role in establishing and maintaining milk production

  2025cites this paper
• Split-Small GTPase Reassembly as a Method to Control Cellular Signaling with User-Defined Inputs

  2025cites this paper
• RHOB regulates megakaryocytic and erythroid differentiation by altering the cell cycle and cytoskeleton

  2025cites this paper
• Split-Small GTPase Reassembly as a Method to Control Cellular Signaling with User-Defined Inputs

  2025cites this paper
• The role of the Rho family small GTPases in regulation of normal and pathological processes

  2024cites this paper
• Mutant KRAS Drives Loss of S100PBP Expression, Enhancing Pancreatic Cancer Progression and Poor Prognosis

  2024cites this paper
• Downregulation of RhoB Inhibits Cervical Cancer Progression and Enhances Cisplatin Sensitivity

  2024cites this paper
• IRTKS Elevation in Patients with Colon Cancer and the Curative Influences of Hamsc Secretome on Polarity and Invasion of HT-29 Colon Cancer Cells

  2024cites this paper
• The Critical Role of the Shroom Family Proteins in Morphogenesis, Organogenesis and Disease

  2024cites this paper
• Role of Rho Family Small GTPases in the Regulation of Normal and Pathological Processes

  2024cites this paper
• ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway

  2023cites this paper
• Helicobacter pylori Eradication Can Reverse Rho GTPase Expression in Gastric Carcinogenesis

  2023cites this paper
• RhoB as a tumor suppressor: It's all about localization.

  2023cites this paper
• Visualizing the subcellular localization of RHOB-GTP and GTPase-Effector complexes using a split-GFP/nanobody labelling assay.

  2023cites this paper
• Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components

  2023cites this paper
• Redox Dysregulation in the Tumor Microenvironment Contributes to Cancer Metastasis

  2023cites this paper
• Antioxidant peptides, the guardian of life from oxidative stress

  2023cites this paper
• Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice

  2023cites this paper
• Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

  2023cites this paper
• Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review.

  2023cites this paper
• Unveiling the Angiogenic Effects of Cannabinoids: Enhancers or inhibitors?

  2023cites this paper
• Brusatol Inhibits Proliferation and Metastasis of Colorectal Cancer by Targeting and Reversing the RhoA/ROCK1 Pathway

  2022cites this paper
• The role of ROS in tumour development and progression

  2022cites this paper
• OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer

  2022cites this paper
• Circ_0084043-miR-134-5p axis regulates PCDH9 to suppress melanoma

  2022cites this paper
• PCDH9 suppresses melanoma proliferation and cell migration

  2022cites this paper
• Activation Mechanism of RhoA Caused by Constitutively Activating Mutations G14V and Q63L

  2022cites this paper
• Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

  2022cites this paper
• The Cytotoxic Necrotizing Factors (CNFs)—A Family of Rho GTPase-Activating Bacterial Exotoxins

  2021cites this paper
• The RHO Family GTPases: Mechanisms of Regulation and Signaling

  2021cites this paper
• The RhoGEF Trio: A Protein with a Wide Range of Functions in the Vascular Endothelium

  2021cites this paper
• Distinct cytosine modification profiles define epithelial-to-mesenchymal cell-state transitions

  2021cites this paper
• ARHGEF10L Promotes Cervical Tumorigenesis via RhoA-Mediated Signaling

  2021influential citation
• Exploring the ‘Dormancy Activation Switch’ in the Tumour Microenvironment for Metastatic Lung Cancer: The Possible Role of MicroRNA

  2021cites this paper
• NDRG1 regulates Filopodia-induced Colorectal Cancer invasiveness via modulating CDC42 activity

  2021cites this paper
• Oncogenic mutations on Rac1 affect global intrinsic dynamics underlying GTP and PAK1 binding.

  2021cites this paper
• Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway

  2021cites this paper
• S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer

  2020cites this paper
• SOX9 Is Essential for Triple-Negative Breast Cancer Cell Survival and Metastasis

  2020cites this paper
• PCDH9 target RAC1/ROS-NADPH-oxidase complex with the assistance of Pyk2 interaction through Cyclin D1 trafficking

  2020cites this paper
• Hormones Secretion and Rho GTPases in Neuroendocrine Tumors

  2020cites this paper
• PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells

  2020cites this paper
• Proteomic Profiling of Archived Tissue of Primary Melanoma Identifies Proteins Associated with Metastasis

  2020cites this paper
• ARHGEF10L expression regulates cell proliferation and migration in gastric tumorigenesis

  2020cites this paper
• Computational and in vitro Pharmacodynamics Characterization of 1A-116 Rac1 Inhibitor: Relevance of Trp56 in Its Biological Activity

  2020cites this paper
• Equine Alphaherpesviruses Require Activation of the Small GTPases Rac1 and Cdc42 for Intracellular Transport

  2020cites this paper
• Combretastatin A-4 disodium phosphate and low dose gamma irradiation suppress hepatocellular carcinoma by downregulating ROCK1 and VEGF gene expression

  2020cites this paper
• CD99 regulates cancer cell transendothelial migration and endothelial cell function via CDC42 and actin remodelling

  2019cites this paper
• Low-dose ionizing radiation attenuates mast cell migration through suppression of monocyte chemoattractant protein-1 (MCP-1) expression by Nr4a2

  2019cites this paper
• Modular regulation of Rho family GTPases in development

  2019cites this paper
• CONEBEAM COMPUTED TOMOGRAPHY IN DIAGNOSIS OF DENTAL PATHOLOGY

  2019cites this paper
• Therapeutic Effect of Y-27632 on Tumorigenesis and Cisplatin-Induced Peripheral Sensory Loss through RhoA–NF-κB

  2019cites this paper
• SHROOM2 inhibits tumor metastasis through RhoA–ROCK pathway-dependent and -independent mechanisms in nasopharyngeal carcinoma

  2019cites this paper
• Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma

  2019cites this paper
• Small GTPase Rab3B: biological properties and possible role in carcinogenesis

  2019cites this paper
• SRC and ERK cooperatively phosphorylate DLC1 and attenuate its Rho-GAP and tumor suppressor functions

  2019cites this paper
• ARHGEF10L contributes to liver tumorigenesis through RhoA‐ROCK1 signaling and the epithelial‐mesenchymal transition

  2019cites this paper
• Role of mTORC1 in intestinal epithelial repair and tumorigenesis

  2019cites this paper
• In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer

  2019cites this paper
• Genomic Divergence in Swedish Warmblood Horses Selected for Equestrian Disciplines

  2019cites this paper
• MicroRNAs Involved in Metastasis of Hepatocellular Carcinoma: Target Candidates, Functionality and Efficacy in Animal Models and Prognostic Relevance

  2019cites this paper
• Role of EFA6B, Exchange Factor of Arf6, in epithelial morphogenesis and collective invasion of human mammary cells

  2019cites this paper
• Reduced RhoA expression enhances breast cancer metastasis with a concomitant increase in CCR5 and CXCR4 chemokines signaling

  2019cites this paper
• The Identification of Differentially Expressed Genes Showing Aberrant Methylation Patterns in Pheochromocytoma by Integrated Bioinformatics Analysis

  2019cites this paper
• Rational drug design of antineoplastic agents using 3D-QSAR, cheminformatic, and virtual screening approaches.

  2019cites this paper
• Systematic characterization of pan‐cancer mutation clusters

  2018cites this paper
• RhoB: Team Oncogene or Team Tumor Suppressor?

  2018cites this paper
• Downregulation of sTarD8 in gastric cancer and its involvement in gastric cancer progression

  2018cites this paper
• Expression profile of stem cell pathway genes in patients with advanced breast cancer after neoadjuvant therapy

  2018cites this paper
• High-content tripartite split-GFP cell-based assays to screen for modulators of small GTPase activation

  2018cites this paper
• Activation of Rho Family GTPases by Small Molecules

  2018cites this paper
• Downregulation of STARD8 in gastric cancer and its involvement in gastric cancer progression

  2018cites this paper
• The Rho GTPase Rnd1 inhibits epithelial–mesenchymal transition in hepatocellular carcinoma and is a favorable anti-metastasis target

  2018cites this paper
• al.Effect of N -acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways' response to oxidative stress in weaned piglets[J].British

  2018cites this paper
• NKCC1 promotes EMT‐like process in GBM via RhoA and Rac1 signaling pathways

  2018cites this paper
• Cdc42 Signaling Pathway Inhibition as a Therapeutic Target in Ras- Related Cancers.

  2017cites this paper
• Heuristic algorithms for feature selection under Bayesian models with block-diagonal covariance structure

  2017cites this paper
• A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer

  2017cites this paper
• Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor

  2017cites this paper
• The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB.

  2017cites this paper
• Total alkaloids of Corydalis saxicola bunting inhibits migration of A549 cells by suppressing Cdc42 or Vav1.

  2017cites this paper
• Extracellular Matrix Induction of Intracellular Reactive Oxygen Species

  2017cites this paper
• Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti‐melanoma immune response

  2017cites this paper
• NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein

  2017cites this paper
• Regulation of HC11 mouse breast epithelial cell differentiation by the E‐cadherin/Rac axis

  2017cites this paper
• Roles of an N-terminal coiled-coil-containing domain in the localization and function of Bem3, a Rho GTPase-activating protein in budding yeast.

  2017cites this paper
• The Role of Hypoxia-Regulated RhoB Expression in Breast Cancer Tumorigenesis and Metastasis

  2017cites this paper
• Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cells

  2017cites this paper
• Arg188 drives RhoC membrane binding

  2017cites this paper
• The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

  2017cites this paper
• Target Prediction Based On PPI Network

  2016cites this paper
• Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion.

  2016cites this paper
• Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

  2016cites this paper
• Cdc 42 and Rac 1 activity is reduced in human pheochromocytoma and 1 correlates with FARP 1 and ARHGEF 1 expression 2 3 4

  2016cites this paper