The role of aquaporin-5 in cancer cell migration: A potential active participant

Jensen, Helene Halkjær; Login, Frédéric H.; Koffman, Jennifer S.; Kwon, Tae‐Hwan; Nejsum, Lene N.

doi:10.1016/j.biocel.2016.09.005

Cited by 45 publications

(35 citation statements)

References 59 publications

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“…AQP5 involvement in mediating fluid transport from the corneal stroma into the tears and contributing to maintaining tear film isotonicity is evident since in AQP5 knockout mice, tear fluid osmolality increased nearly two-fold 6 . Besides its involvement in offsetting osmotic stresses that disrupt tissue homeostasis, there is emerging evidence that AQP5 overexpression contributes to promoting increases in inflammation, cell proliferation, and migration in cervical, colon and gastric cancer 7–9 . Furthermore, AQP5 upregulation is associated with the development of airway inflammation and mucous hypersecretion during chronic asthma 10 .…”

Section: Introductionmentioning

confidence: 99%

Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells

Ren

Reinach

et al. 2017

Sci Rep

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Tear film hyperosmolarity and anterior ocular inflammation are two clinical signs that may be indicative of dry eye disease (DED). This condition can cause pathological and functional changes to the anterior ocular surface tissues. A contributing factor may be dysfunctional aquaporin 5 (AQP5) water channels as they are the AQP subtype that expressed in the corneal epithelium and contribute to fluid efflux needed for corneal function. We determined if described hyperosmolarity-induced increases in proinflammatory cytokine expression and cell death are mediated through AQP5 upregulation and JNK1/2 MAPK signaling activation in both primary human corneal epithelial cells (HCECs), and in a HCEC line. Real time RT-PCR identified rises in IL-1β, IL-6, IL-8, TNF-α, caspase-1, and AQP5 mRNA levels upon step increases in osmolarity up to 550 mOsm. Western blot analysis and the TUNEL assay identified corresponding rises in AQP5 and p-JNK1/2 protein expression and cell death respectively. JNK1/2 inhibition with SP600125, or siRNA AQP5 gene silencing reduced hypertonic-induced rises in proinflammatory cytokine expression and cell death. Taken together, hypertonicity-induced AQP5 upregulation leads to increases in proinflammatory cytokine expression and cell death through JNK1/2 MAPK activation. These results suggest that drug targeting AQP5 upregulation may be a therapeutic option in DED management.

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Section: Introductionmentioning

confidence: 99%

Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells

Ren

Reinach

et al. 2017

Sci Rep

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“…increased the expression of genes and their corresponding proteins that are involved in cell migration (46)(47)(48)(49), such as AQP5, MMP9, vimentin, and fibronectin. In contrast, FBX cotreatment importantly mitigated the LDL-or HCDinduced up-regulation of these genes and proteins.…”

mentioning

confidence: 99%

The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia

Choi

et al. 2019

FASEB j.

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Hypercholesterolemia is reported to increase reactive oxygen species (ROS) and to promote breast cancer progression. ROS play an important role in tumor biology, and xanthine oxidase (XO) is an enzyme that generates ROS. The effects of febuxostat (FBX), an XO inhibitor, on breast cancer cell migration under LDL stimulation in vitro and metastasis of breast cancer associated with hypercholesterolemia in vivo were studied. In vitro, FBX significantly inhibited LDL‐induced ROS production and cell migration. Treatment of small interfering RNA against XO was consistent with the findings of FBX treatment. In vivo, a significant increase of tumor growth and pulmonary metastasis was observed in a xenograft mouse model with 4T1 cells on a high cholesterol diet (HCD), both of which were markedly inhibited by FBX or allopurinol treatment. Moreover, ERK represented the main target‐signaling pathway that was affected by FBX treatment in a xenograft mouse model on an HCD evaluated by NanoString nCounter analysis. Consistently, MEK/ERK inhibitors directly decreased the LDL‐induced cell migration in vitro. In conclusion, FBX mitigates breast cancer cell migration and pulmonary metastasis in the hyperlipidemic condition, associated with decreased ROS generation and MAPK phosphorylation. The inhibition of ERK pathways is likely to underlie the XO inhibitor‐mediated suppression of breast cancer cell migration.—Oh, S.‐H., Choi, S.‐Y., Choi, H.‐J., Ryu, H.‐M., Kim, Y.‐J., Jung, H.‐Y., Cho, J.‐H., Kim, C.‐D., Park, S.‐H., Kwon, T.‐H., Kim, Y.‐L. The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia. FASEB J. 33, 7301–7314 (2019). http://www.fasebj.org

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“…Moreover, AQPs are implicated in carcinogenesis of multiple cancers and are reported to be pivotal in metastasis (47,52,53). In previous studies, we showed that increased expression of AQP5 in breast cancer was associated with enhanced cancer cell migration, metastasis, and poor prognosis in human patients (5,6).…”

Section: Discussionmentioning

confidence: 93%

Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

Jensen

Pedersen

et al. 2019

FASEB j.

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Plasticity of epithelial cell‐cell adhesion is vital in epithelial homeostasis and is regulated in multiple processes associated with cell migration, such as embryogenesis and wound healing. In cancer, cell‐cell adhesion is compromised and is associated with increased cell migration and metastasis. Aquaporin (AQP) water channels facilitate water transport across cell membranes and are essential in the regulation of body water homeostasis. Increased expression of several AQPs, especially AQP5, is associated with increased cancer cell migration, metastasis, and poor prognosis. We found that AQP5 overexpression in normal epithelial cells induced cell detachment and dissemination from migrating cell sheets. AQP5 reduced both cell‐cell coordination during collective migration and overall distance covered by the migrating cell sheets. AQP5 and the isoforms AQP1 and AQP4 decreased, whereas AQP3 increased, levels of plasma membrane‐associated lateral junctional proteins. This regulation was mediated by the cytoplasmic domains of the AQPs. This shows that the AQPs have dual functions in epithelial physiology: as channel proteins and as differential regulators of cell‐cell adhesiveness. This regulation may contribute to dynamic regulation of cell junctions in processes such as embryogenesis and wound healing and also explain the pivotal roles of AQPs in carcinogenesis and metastasis.—Login, F. H., Jensen, H. H., Pedersen, G. A., Koffman, J. S., Kwon, T.‐H., Parsons, M., Nejsum, L. N. Aquaporins differentially regulate cell‐cell adhesion in MDCK cells. FASEB J. 33, 6980–6994 (2019). http://www.fasebj.org

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The role of aquaporin-5 in cancer cell migration: A potential active participant

Cited by 45 publications

References 59 publications

Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells

Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells

The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia

Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

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