TY - JOUR
T1 - Aquaporins differentially regulate cell-cell adhesion in MDCK cells
AU - Login, Frédéric H.
AU - Jensen, Helene H.
AU - Pedersen, Gitte A.
AU - Koffman, Jennifer S.
AU - Kwon, Tae Hwan
AU - Parsons, Maddy
AU - Nejsum, Lene N.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - cancer
KW - cell migration
KW - junctional proteins
KW - metastasis
UR - http://www.scopus.com/inward/record.url?scp=85067309602&partnerID=8YFLogxK
U2 - 10.1096/fj.201802068RR
DO - 10.1096/fj.201802068RR
M3 - Article
C2 - 30840830
AN - SCOPUS:85067309602
SN - 1530-6860
VL - 33
SP - 6980
EP - 6994
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 6
ER -
