Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

Login, Frédéric H.; Jensen, Helene Halkjær; Pedersen, Gitte A.; Koffman, Jennifer S.; Kwon, Tae Hwan; Parsons, Maddy; Nejsum, Lene N.

doi:10.1096/fj.201802068rr

Cited by 30 publications

(36 citation statements)

References 60 publications

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“…Moreover, a positive tendency in the correlation analysis between AQP5 and Rac‐GTP expression was reported in human breast cancer tissue, the latter being a GTPase involved in cell migration . Also, AQP5 overexpression in normal epithelial cells (MDCK cells) stimulated cell detachment and dissemination from migrating cell sheets, which could be counteracted by inhibition of Ras . These findings indicated that AQP5 contributes to cancer cell migration,and it is an important prognostic marker protein for breast cancer …”

Section: Introductionmentioning

confidence: 82%

“…16 Also, AQP5 overexpression in normal epithelial cells (MDCK cells) stimulated cell detachment and dissemination from migrating cell sheets, which could be counteracted by inhibition of Ras. 17 These findings indicated that AQP5 contributes to cancer cell migration,and it is an important prognostic marker protein for breast cancer. 13,14,18 MicroRNA (miRNA), the small non-coding RNAs of approximately 20-22 nucleotides in length, regulates mRNA stability by interacting with the complementary sequence motif of the 3ʹ-untranslated region (UTR) of the target mRNA.…”

Section: Introductionmentioning

confidence: 87%

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Exosomes co‐expressing AQP5‐targeting miRNAs and IL‐4 receptor‐binding peptide inhibit the migration of human breast cancer cells

et al. 2020

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Aquaporin‐5 (AQP5) plays a role in breast cancer cell migration. This study aimed to identify AQP5‐targeting miRNAs and examine their effects on breast cancer cell migration through exosome‐mediated delivery. Bioinformatic analyses identified miR‐1226‐3p, miR‐19a‐3p, and miR‐19b‐3p as putative regulators of AQP5 mRNA. Immunoblotting revealed a decrease of AQP5 protein abundance when each of these miRNAs was transfected into human breast cancer MDA‐MB‐231 cells. Quantitative real‐time PCR demonstrated the reduction of AQP5 mRNA expression by the transfection of miR‐1226‐3p and a luciferase reporter assay revealed the reduction of AQP5 translation after the transfection of miR‐19b‐3p in MDA‐MB‐231 cells. Consistently, the transfection of each miRNA impeded cell migration. Pathway enrichment analyses showed that these three miRNAs regulate target genes, which were predominantly enriched in the gap junction pathway. For the efficient delivery of AQP5‐targeting miRNAs to breast cancer cells, exosomes expressing both miRNAs and a peptide targeting interleukin‐4 receptor, which is highly expressed in breast cancer cells, were bioengineered and their inhibitory effects on AQP5 protein expression and cell migration were demonstrated in MDA‐MB‐231 cells. Taken together, AQP5‐regulating miRNAs are identified, which could be exploited for the inhibition of breast cancer cell migration via the exosome‐mediated delivery.

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Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 87%

Exosomes co‐expressing AQP5‐targeting miRNAs and IL‐4 receptor‐binding peptide inhibit the migration of human breast cancer cells

et al. 2020

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“…In addition to the major involvement of AQP5 in saliva secretion, AQP5 and other AQPs might likely be implicated in cell proliferation and migration, neuronal signaling, adhesion and apoptosis occurring during SG embryonic development [ 18 , 26 , 43 , 44 ]. The individual role of AQPs in SG embryonic development requires further studies.…”

Section: Physiological Function Of the Aqps In Sgmentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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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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Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

Cited by 30 publications

References 60 publications

Exosomes co‐expressing AQP5‐targeting miRNAs and IL‐4 receptor‐binding peptide inhibit the migration of human breast cancer cells

Exosomes co‐expressing AQP5‐targeting miRNAs and IL‐4 receptor‐binding peptide inhibit the migration of human breast cancer cells

Insight into Salivary Gland Aquaporins

Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions

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