The potential roles of aquaporin 4 in malignant gliomas

Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous system and is primarily expressed in astrocytes. Recently, accumulated evidence has pointed to AQP4 as a key molecule that could play a critical role in glioma development. Discoveries of the role of AQP4 in cell migration suggest that AQP4 could be a significant factor regarding glioma malignancies. However, the AQP4 expression levels in glioma have not been fully elucidated; furthermore, the correlation of AQP4 expression with glioma malignancy remains controversial. Here, we review the expression pattern and predictive significance of AQP4 in malignant glioma. The molecular mechanism of AQP4 as it pertains to the migration and invasion of human glioma cells has been summarized. In addition, the important roles of AQP4 in combating drug resistance as well as potential pharmacological blockers of AQP4 have been systematically discussed. More research should be conducted to elucidate the potential roles of AQP4 in malignant glioma for identifying the tumor type, progression stages and optimal treatment strategies. The observed experimental results strongly emphasize the importance of this topic for future investigations.

• Publication year

  2017

• Venue

  OncoTarget

• Publication date

  2017-03-08

• Fields of study

  Medicine

• Identifiers
  DOI 10.18632/oncotarget.16017PMID 28423683PMCID 5458289
• 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.

• Key roles of aquaporins in tumor biology.

  2015cited by this paper
• Effects of propofol and sevoflurane on aquaporin-4 and aquaporin-9 expression in patients performed gliomas resection.

  2015cited by this paper
• Aquaporins as diagnostic and therapeutic targets in cancer: How far we are?

  2015cited by this paper
• Aquaporins: important but elusive drug targets

  2014cited by this paper
• Knockdown a Water Channel Protein, Aquaporin-4, Induced Glioblastoma Cell Apoptosis

  2013cited by this paper
• In Vivo NADH Fluorescence Imaging Indicates Effect of Aquaporin-4 Deletion on Oxygen Microdistribution in Cortical Spreading Depression

  2013cited by this paper
• Effect of Propofol Post-treatment on Blood–Brain Barrier Integrity and Cerebral Edema After Transient Cerebral Ischemia in Rats

  2013cited by this paper
• Tumor-associated edema in brain cancer patients: pathogenesis and management

  2013cited by this paper
• Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4

  2013cited by this paper
• An Allograft Glioma Model Reveals the Dependence of Aquaporin-4 Expression on the Brain Microenvironment

  2012cited by this paper
• Deletion of aquaporin‐4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier

  2012cited by this paper
• Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma

  2012cited by this paper
• Aquaporin 4 and neuromyelitis optica.

  2012cited by this paper
• Differential expression of MMP-9 and AQP4 in human glioma samples.

  2012cited by this paper
• The disturbed blood-brain barrier in human glioblastoma.

  2012influential reference
• Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid-based photodynamic treatment. Laboratory investigation.

  2011cited by this paper
• Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro

  2011cited by this paper
• Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells.

  2011cited by this paper
• Selective enrichment of hypericin in malignant glioma: pioneering in vivo results.

  2011cited by this paper
• Expression of aquaporin-4 in human supratentorial meningiomas with peritumoral brain edema and correlation of VEGF with edema formation.

  2011cited by this paper
• Propofol improved neurobehavioral outcome of cerebral ischemia-reperfusion rats by regulating Bcl-2 and Bax expression.

  2011cited by this paper
• Changes in Brain &bgr;-Amyloid Deposition and Aquaporin 4 Levels in Response to Altered Agrin Expression in Mice

  2011cited by this paper
• The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction

  2010cited by this paper
• Water permeability through aquaporin-4 is regulated by protein kinase C and becomes rate-limiting for glioma invasion.

  2010cited by this paper
• AQP-4 in peritumoral edematous tissue is correlated with the degree of glioma and with expression of VEGF and HIF-alpha

  2010influential reference
• Regulation of brain aquaporins.

  2010cited by this paper
• Roles for novel pharmacological blockers of aquaporins in the treatment of brain oedema and cancer

  2010influential reference
• Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema

  2010cited by this paper
• Aquaporin-4 in glioma invasion and an analysis of molecular mechanisms.

  2010cited by this paper
• Identification of aquaporin 4 inhibitors using in vitro and in silico methods.

  2009cited by this paper
• AQP4 gene deletion in mice does not alter blood-brain barrier integrity or brain morphology.

  2009cited by this paper
• Acetazolamide reversibly inhibits water conduction by aquaporin-4.

  2009cited by this paper
• Agrin, Aquaporin-4, and Astrocyte Polarity as an Important Feature of the Blood-Brain Barrier

  2009cited by this paper
• Sporadic obstructive hydrocephalus in Aqp4 null mice

  2009cited by this paper
• Agrin defines polarized distribution of orthogonal arrays of particles in astrocytes

  2009cited by this paper
• Inhibition of aquaporin 4 by antiepileptic drugs.

  2009cited by this paper
• Intrathecal pathogenic anti–aquaporin‐4 antibodies in early neuromyelitis optica

  2009cited by this paper
• Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site

  2009cited by this paper
• The sodium pump alpha1 subunit as a potential target to combat apoptosis-resistant glioblastomas.

  2008cited by this paper
• AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells

  2008cited by this paper
• Altered blood–brain barrier integrity in adult aquaporin-4 knockout mice

  2008cited by this paper
• Lack of aquaporin-4 water transport inhibition by antiepileptics and arylsulfonamides.

  2008cited by this paper
• AQP4 expression in striatal primary cultures is regulated by dopamine – implications for proliferation of astrocytes

  2008cited by this paper
• Intracerebral VEGF injection highly upregulates AQP4 mRNA and protein in the perivascular space and glia limitans externa.

  2008cited by this paper
• Test of blockers of AQP1 water permeability by a high-resolution method: no effects of tetraethylammonium ions or acetazolamide

  2008cited by this paper
• Greatly impaired migration of implanted aquaporin‐4‐deficient astroglial cells in mouse brain toward a site of injury

  2007cited by this paper
• Expression pattern of the water channel aquaporin‐4 in human gliomas is associated with blood–brain barrier disturbance but not with patient survival

  2007influential reference
• Aquaporin-4 and brain edema

  2007cited by this paper
• Identification of arylsulfonamides as Aquaporin 4 inhibitors.

  2007cited by this paper
• Expression and function of water channels (aquaporins) in migrating malignant astrocytes

  2007cited by this paper
• Malignant astrocytic glioma: genetics, biology, and paths to treatment.

  2007cited by this paper
• Quaternary Ammonium Compounds as Water Channel Blockers

  2006cited by this paper
• Modulation of AQP4 expression by the protein kinase C activator, phorbol myristate acetate, decreases ischemia-induced brain edema.

  2006cited by this paper
• Astrocyte–endothelial interactions at the blood–brain barrier

  2006cited by this paper
• Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology

  2006cited by this paper
• Implications of the aquaporin-4 structure on array formation and cell adhesion.

  2006cited by this paper
• Hypoxia‐induced astrocytic reaction and increased vascular permeability in the rat cerebellum

  2006cited by this paper
• Decompressive craniectomy for severe head injury in patients with major extracranial injuries.

  2006cited by this paper
• Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption

  2005cited by this paper
• Involvement of aquaporin-4 in astroglial cell migration and glial scar formation

  2005cited by this paper
• Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule.

  2005cited by this paper
• Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low- and high-grade human brain tumors

  2005cited by this paper
• Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.

  2005cited by this paper
• New possible roles for aquaporin‐4 in astrocytes: cell cytoskeleton and functional relationship with connexin43

  2005cited by this paper
• A role for ion channels in glioma cell invasion.

  2005cited by this paper
• Cell polarization mechanisms during directed cell migration

  2005cited by this paper
• Regulation of brain aquaporins.

  2004cited by this paper
• Genetic Pathways to Glioblastoma

  2004cited by this paper
• Increased seizure threshold in mice lacking aquaporin-4 water channels

  2004cited by this paper
• Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edema

  2004cited by this paper
• Ion channels and amino acid transporters support the growth and invasion of primary brain tumors

  2004cited by this paper
• Molecular mechanisms of brain tumor edema.

  2004cited by this paper
• Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae

  2004influential reference
• Increased seizure duration in mice lacking aquaporin-4 water channels.

  2004cited by this paper
• Increased aquaporin-4 expression in ammonia-treated cultured astrocytes

  2003cited by this paper
• Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms

  2003cited by this paper
• The lamellipodium: where motility begins.

  2002cited by this paper
• Aquaporin-4 expression is increased in oedematous human brain tumours

  2002cited by this paper
• Aquaporins in the central nervous system.

  2001cited by this paper
• Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke

  2000cited by this paper
• Wnt signaling and cancer.

  2000cited by this paper
• Increased blood–brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor

  1998cited by this paper
• Expression and distribution of vascular endothelial growth factor protein in human brain tumors

  1997influential reference
• Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema.

  1997cited by this paper
• Biochemical Characterization of the Stimulatory Effects of Halothane and Propofol on Purified Brain Protein Kinase C

  1995cited by this paper
• Glia-Neuronal and Glia-Vascular Interrelations in Blood-Brain Barrier Formation and Axon Regeneration in Vertebrates

  1995cited by this paper
• Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex.

  1995cited by this paper
• Orthogonal arrays of intramembranous particles: a review with special reference to astrocytes.

  1995cited by this paper
• Electron microscopy of the blood‐brain barrier in disease

  1994cited by this paper
• Tumor invasion and metastasis: an imbalance of positive and negative regulation.

  1991cited by this paper
• Patient age, histologic features, and length of survival in patients with glioblastoma multiforme

  1987cited by this paper
• Bumetanide inhibits (Na + K + 2Cl) co-transport at a chloride site.

  1983cited by this paper

• Interplay of Neuroinflammation and Epilepsy in Glioblastoma Multiforme: Mechanisms and Therapeutic Implications

  2025cites this paper
• Modeling Bioelectric State Transitions in Glial Cells: An ASAL-Inspired Computational Approach to Glioblastoma Initiation

  2025cites this paper
• Aquaporin-4 in glioblastoma: a nexus of glymphatic dysfunction, edema, immune evasion, and treatment resistance

  2025cites this paper
• CGF-Conditioned Medium Modulates Astrocytic Differentiation and Invasiveness in U87MG Glioblastoma Cells

  2025cites this paper
• E3 ubiquitin ligase BTRC inhibits the proliferation and tumor growth of glioma cells through the NFAT5/AQP4 axis

  2025cites this paper
• Size of aquaporin-4 orthogonalarraysofparticlesareaffectedbythe palmitoylation state ofthe M1 isoform.

  2025cites this paper
• Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood–Brain Barrier and Blood–Tumor Barrier

  2025cites this paper
• Disruption of the Blood-Brain Barrier of the Prefrontal Cortex in Peripheral Tumor Growth and Correction with Lithium Carbonate

  2025cites this paper
• Proteomic Analysis of the Low Molecular Mass Fraction of Newly Diagnosed and Recurrent Glioblastoma CUSA Fluid: A Pilot Investigation of the Peptidomic Profile

  2025cites this paper
• Methylation and gene expression patterns in adamantinomatous craniopharyngioma highlight a panel of genes associated with disease progression-free survival

  2025cites this paper
• Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma

  2024cites this paper
• Harnessing Arsenic Derivatives and Natural Agents for Enhanced Glioblastoma Therapy

  2024cites this paper
• Update on the intriguing roles of AQP4 expression and redistribution in the progression and treatment of glioma

  2024influential citation
• Aquaporins in colorectal cancer: exploring their role in tumorigenesis, metastasis, and drug response

  2024cites this paper
• Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach

  2024cites this paper
• Thermodynamics and S-Palmitoylation Dependence of Interactions between Human Aquaporin-4 M1 Tetramers in Model Membranes

  2024cites this paper
• Ion Channels in Gliomas—From Molecular Basis to Treatment

  2023cites this paper
• Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema

  2023cites this paper
• Biogenic Imaging Contrast Agents

  2023cites this paper
• Leukemia-derived Exosomes Can Induce Responses Related to Tumorigenesis on Non-tumoral Astrocytes

  2023cites this paper
• AQP4 as a new potential molecular biomarker for prognosis of LGG: comprehensive analysis based on online platforms.

  2023cites this paper
• The Consistence of Dynamic Contrast‐Enhanced MRI and Filter‐Exchange Imaging in Measuring Water Exchange Across the Blood–Brain Barrier in High‐Grade Glioma

  2023cites this paper
• Aquaporins in Tumor.

  2023cites this paper
• Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients

  2022cites this paper
• Nanomedicine for Brain Cancer.

  2022cites this paper
• The Characterization of Structure and Prediction for Aquaporin in Tumour Progression by Machine Learning

  2022cites this paper
• Deciphering the Role of Aquaporins in Metabolic Diseases: A Mini Review.

  2022cites this paper
• Glioblastoma Stem-like Cell Detection Using Perfusion and Diffusion MRI

  2022influential citation
• Blood-Brain Barrier Alterations and Edema Formation in Different Brain Mass Lesions

  2022cites this paper
• The Water Transport System in Astrocytes–Aquaporins

  2022cites this paper
• AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles

  2022cites this paper
• AQP4, Astrogenesis, and Hydrocephalus: A New Neurological Perspective

  2022cites this paper
• Epileptogenesis and Tumorigenesis in Glioblastoma: Which Relationship?

  2022cites this paper
• Fast‐field‐cycling NMR at very low magnetic fields: water molecular dynamic biomarkers of glioma cell invasion and migration

  2021cites this paper
• Aquaporin 4 and its Relationship with Brain Astrocytomas – Literature Review

  2021cites this paper
• The Expression of Aquaporin-1 and Aquaporin-3 in Extrahepatic Cholangiocarcinoma and their Clinicopathological Significance.

  2021cites this paper
• Dynamics of AQP4 upon exposure to seropositive patient serum before and after Rituximab therapy in Neuromyelitis Optica: A cell-based study.

  2021cites this paper
• The relationship between diffusion heterogeneity and microstructural changes in high-grade gliomas using Monte Carlo simulations.

  2021cites this paper
• Old Stars and New Players in the Brain Tumor Microenvironment

  2021cites this paper
• Multi-project and Multi-profile joint Non-negative Matrix Factorization for cancer omic datasets

  2021cites this paper
• Evaluation of surgical resection combined with interstitial sustained-release chemotherapy in the treatment of recurrent malignant gliomas.

  2021cites this paper
• A Bioinformatics Analysis of the Potential Roles of Aquaporin 4 in Human Brain Tumors: An Immune-Related Process

  2021cites this paper
• Aquaporins implicated in the cell proliferation and the signaling pathways of cell stemness.

  2021cites this paper
• Aquaporins and diseases pathogenesis: From trivial to undeniable involvements, a disease‐based point of view

  2021cites this paper
• Rapid 3D Bioprinting of Glioblastoma Model Mimicking Native Biophysical Heterogeneity.

  2021cites this paper
• Pathway-based deep clustering for molecular subtyping of cancer.

  2020cites this paper
• Deep learning to classify single-cell RNA sequencing in primary glioblastoma

  2020cites this paper
• Inhibition of lncRNA LINC00461/miR-216a/aquaporin 4 pathway suppresses cell proliferation, migration, invasion, and chemoresistance in glioma

  2020cites this paper
• Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

  2020cites this paper
• Expression of Olig2, Nestin, NogoA and AQP4 have no impact on overall survival in IDH-wildtype glioblastoma

  2020cites this paper
• Radiation-Induced Changes in Tumor Vessels and Microenvironment Contribute to Therapeutic Resistance in Glioblastoma

  2019cites this paper
• AQP4 Aggregation State Is a Determinant for Glioma Cell Fate.

  2019cites this paper
• Cerebrospinal fluid flow. Part 2. Aquaporins and their role in CNS water homeostasis

  2019cites this paper
• Aquaporins Involvement in Pancreas Physiology and in Pancreatic Diseases

  2019cites this paper
• Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics

  2019cites this paper
• Review: Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder

  2019cites this paper
• Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794

  2019cites this paper
• Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

  2019cites this paper
• LINE-2 transposable elements are a source of functional human microRNAs and target sites

  2019cites this paper
• miRNA-320a inhibits glioma cell invasion and migration by directly targeting aquaporin 4.

  2018cites this paper
• Water transport proteins–aquaporins (AQPs) in cancer biology

  2018cites this paper
• Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in human glioblastoma

  2018cites this paper
• Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  2017cites this paper
• Bone morphogenetic protein-4 signalling in glial cells of the central nervous system

  2017cites this paper
• LINE-2 transposable elements shape post-transcriptional gene regulation in the human brain

  2017cites this paper