Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity
Por:
Verdejo-Torres O., Flores-Maldonado C., Padilla-Benavides T., Campos-Blázquez J.P., Lara-Lemus R., Perez Salazar E., Cereijido M., Contreras R.G.
Publicada:
1 ene 2019
Resumen:
Studies made in the Madin-Darby canine kidney (MDCK) epithelial cell line showed that ouabain regulates cell adhesion and cell-adhesion-related biological processes, such as migration. Here, we demonstrated that 10 nM ouabain accelerates collective cell migration and heals wounds in cultured MDCK cell monolayers. Ouabain-induced acceleration of cell migration depends on activation of the cSrc-ERK1/2 signaling cascade, as it was inhibited by the kinase inhibitors PP2 and PD98059. Activation of the cSrc-ERK1/2 signaling cascade increased expression and activation of the extracellular matrix metalloproteinase-2 (MMP-2). Inhibition of MMP activity using the generic inhibitor GM6001 or the potent iMMP-2 inhibitor prevented the accelerative effect of ouabain. Likewise, Focal Adhesion Kinase (FAK) inhibition with the transfection of dominant negative peptide FRNK impaired the effect of ouabain. These results suggest that ouabain binding to the Na + ,K + -ATPase accelerates collective migration of MDCK cells through activation of the cSrc-ERK1/2-FAK signaling cascade and promoting secretion and MMP activity. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Filiaciones:
Verdejo-Torres O.:
Departamento of Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City, D.F. 07360, Mexico
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States
Flores-Maldonado C.:
Departamento of Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City, D.F. 07360, Mexico
Padilla-Benavides T.:
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States
Campos-Blázquez J.P.:
Departamento of Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City, D.F. 07360, Mexico
Lara-Lemus R.:
Department of Biochemical Investigation, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Calz. De Tlalpan 4502, col. Sección XVI, Tlalpan, México City, 14080, Mexico
Perez Salazar E.:
Department of Cell Biology, Center for Research and Advanced Studies (CINVESTAV), Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico
Cereijido M.:
Departamento of Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City, D.F. 07360, Mexico
Contreras R.G.:
Departamento of Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City, D.F. 07360, Mexico
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