Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
Open Access
- 1 June 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 9 (6), 1515-1524
- https://doi.org/10.1158/1535-7163.mct-09-0832
Abstract
Epithelial-to-mesenchymal transition (EMT) is an important developmental process, participates in tissue repair, and occurs during pathologic processes of tumor invasiveness, metastasis, and tissue fibrosis. The molecular mechanisms leading to EMT are poorly understood. Although it is well documented that transforming growth factor (TGF)-β plays a central role in the induction of EMT, the targets of TGF-β signaling are poorly defined. We have shown earlier that Na,K-ATPase β1-subunit levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. In this study, we provide evidence that Na,K-ATPase is a new target of TGF-β1–mediated EMT in renal epithelial cells, a model system used in studies of both cancer progression and fibrosis. We show that following treatment with TGF-β1, the surface expression of the β1-subunit of Na,K-ATPase is reduced, before well-characterized EMT markers, and is associated with the acquisition of a mesenchymal phenotype. RNAi-mediated knockdown confirmed the specific involvement of the Na,K-ATPase β1-subunit in the loss of the epithelial phenotype and exogenous overexpression of the Na,K-ATPase β1-subunit attenuated TGF-β1–mediated EMT. We further show that both Na,K-ATPase α- and β-subunit levels are highly reduced in renal fibrotic tissues. These findings reveal for the first time that Na,K-ATPase is a target of TGF-β1–mediated EMT and is associated with the progression of EMT in cancer and fibrosis. Mol Cancer Ther; 9(6); 1515–24. ©2010 AACR.Keywords
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This publication has 51 references indexed in Scilit:
- The basics of epithelial-mesenchymal transitionJCI Insight, 2009
- Biomarkers for epithelial-mesenchymal transitionsJCI Insight, 2009
- Cell size and invasion in TGF-β–induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathwayThe Journal of cell biology, 2007
- Genetic control of single lumen formation in the zebrafish gutNature, 2007
- The α1 subunit of the sodium pump could represent a novel target to combat non‐small cell lung cancersThe Journal of Pathology, 2007
- Inhibition of Transforming Growth Factor-β Signaling in Normal Lung Epithelial Cells Confers Resistance to Ionizing RadiationInternational Journal of Radiation Oncology*Biology*Physics, 2007
- Janus Model of The Na,K-ATPase β-Subunit Transmembrane Domain: Distinct Faces Mediate α/β Assembly and β-β Homo-oligomerizationJournal of Molecular Biology, 2007
- Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenanceThe Journal of cell biology, 2007
- A pump-independent function of the Na,K-ATPase is required for epithelial junction function and tracheal tube-size controlDevelopment, 2007
- Smad-dependent and Smad-independent pathways in TGF-β family signallingNature, 2003