Effects of dexamethasone on C6 cell proliferation, migration and invasion through the upregulation of AQP1

Guan, Ying; Chen, Jianqiang; Zhan, Yongli; Lu, Hong

doi:10.3892/ol.2018.8269

Cited by 20 publications

(19 citation statements)

References 46 publications

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“…Glioma invasiveness has been linked to AQP1 overexpression [ 73 ], which is greater in migrating cells than in the tumor core [ 68 ]. Dexamethasone, which promotes AQP1 transcription, increases the invasiveness of glioma cells [ 74 , 75 ].…”

Section: Resultsmentioning

confidence: 99%

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

Chow

Bowen

Yool

2020

Cancers

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Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of AQP expression and survival rates for patients were evaluated by systematic review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange. AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.

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Section: Resultsmentioning

confidence: 99%

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

Chow

Bowen

Yool

2020

Cancers

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“…Necrotic death of C6 cells can be induced by serum deprivation and DEX enhanced this cytotoxic effect through GR activation (Morita et al, 1999). In the same cell line, the anti-proliferative effect of DEX was shown to be dose and time dependent and to involve Aquaporin 1 (AQP 1 ; Guan et al, 2018). Indeed, DEX increased the mRNA and protein expression of AQP 1 .…”

Section: The Anti- and Pro-proliferative Effects Of Dexmentioning

confidence: 99%

“…Indeed, DEX increased the mRNA and protein expression of AQP 1 . Moreover, the effect of DEX on cell proliferation was abolished upon AQP 1 gene silencing (Guan et al, 2018). Surprisingly, by using U373 cells, Gündisch et al (2012) showed a pro-proliferative effect of DEX (Table 1).…”

Section: The Anti- and Pro-proliferative Effects Of Dexmentioning

confidence: 99%

Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

Cenciarini

Valentino

Belia

et al. 2019

Front. Mol. Neurosci.

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Glioblastoma multiforme (GBM) is the most common and malignant of the glial tumors. The world-wide estimates of new cases and deaths annually are remarkable, making GBM a crucial public health issue. Despite the combination of radical surgery, radio and chemotherapy prognosis is extremely poor (median survival is approximately 1 year). Thus, current therapeutic interventions are highly unsatisfactory. For many years, GBM-induced brain oedema and inflammation have been widely treated with dexamethasone (DEX), a synthetic glucocorticoid (GC). A number of studies have reported that DEX also inhibits GBM cell proliferation and migration. Nevertheless, recent controversial results provided by different laboratories have challenged the widely accepted dogma concerning DEX therapy for GBM. Here, we have reviewed the main clinical features and genetic and epigenetic abnormalities underlying GBM. Finally, we analyzed current notions and concerns related to DEX effects on cerebral oedema, cancer cell proliferation and migration and clinical outcome.

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“…During development and organogenesis, cell proliferation, migration, invasion, and cell-cell adhesion are frequently occurred. In these processes, AQP1, AQP3, and AQP4 have been suggested to be involved in such cellular processes [20][21][22][23][24]. Therefore, AQP5 may also play an important role in these developmental processes, although it is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions

Hosoi

Yao

Hasegawa

et al. 2020

IJMS

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Aquaporin 5 (AQP5) plays an important role in the salivary gland function. The mRNA and protein for AQP5 are expressed in the acini from embryonic days E13-16 and E17-18, respectively and for entire postnatal days. Ligation-reopening of main excretory duct induces changes in the AQP5 level which would give an insight for mechanism of regeneration/self-duplication of acinar cells. The AQP5 level in the submandibular gland (SMG) decreases by chorda tympani denervation (CTD) via activation autophagosome, suggesting that its level in the SMG under normal condition is maintained by parasympathetic nerve. Isoproterenol (IPR), a β-adrenergic agonist, raised the levels of membrane AQP5 protein and its mRNA in the parotid gland (PG), suggesting coupling of the AQP5 dynamic and amylase secretion-restoration cycle. In the PG, lipopolysaccharide (LPS) is shown to activate mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalings and potentially downregulate AQP5 expression via cross coupling of activator protein-1 (AP-1) and NF-κB. In most species, Ser-156 and Thr-259 of AQP5 are experimentally phosphorylated, which is enhanced by cAMP analogues and forskolin. cAMP-dependent phosphorylation of AQP5 does not seem to be markedly involved in regulation of its intracellular trafficking but seems to play a role in its constitutive expression and lateral diffusion in the cell membrane. Additionally, Ser-156 phosphorylation may be important for cancer development.Int. J. Mol. Sci. 2020, 21, 1182 2 of 15 proteins having a tandem repeat structure. The molecule has two Asp-Pro-Ala sequences (NPA motif) that form a hemi-channel structure. These structures face each other from inside and outside of the plasma membrane forming a pore through which water can go through. Within the molecule, there are phosphorylation target motifs as well as glycosylation target ones both of them would play pivotal roles in their functions. Today, it is known that AQPs are present in many living organisms; that is, from animals and plants to microorganisms [3]. It is also known that one or several species of AQPs are expressed in individual tissue. Lines of evidence revealed in the last decade have highlighted the diverse function of AQPs beyond water homeostasis [4,5]. Especially data from knock-out experiments, support the involvement of AQPs in brain edema, cell migration, and others, implying that modulation of AQP function or expression could have therapeutic potential [6].Among various mammalian tissues, kidney convoluted tubule epithelial cells and the salivary gland acinus as well as other exocrine gland tissues transport a large amount of water. In the salivary gland tissues AQP5 is a key water channel like other exocrine glands. Moreover, studies using the AQP5-mutant rat [7], AQP5-knockout mice [8], and Sjögren's syndrome [9] and its model mouse of [10] have suggested that AQP5 plays an important role in maintaining the normal physiologyl of the salivary gland. In this review, we focus dynamic changes of AQP5 in the s...

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Effects of dexamethasone on C6 cell proliferation, migration and invasion through the upregulation of AQP1

Cited by 20 publications

References 46 publications

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

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

Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions

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