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Data from Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
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Data from Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
Data from Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
SR
Sigrid A. Rajasekaran
Sigrid A. Rajasekaran
TH
Thu P. Huynh
Thu P. Huynh
DW
Daniel G. Wolle
Daniel G. Wolle
CE
Cromwell E. Espineda
Cromwell E. Espineda
LI
Landon J. Inge
Landon J. Inge
AS
Anna Skay
Anna Skay
CL
Charles Lassman
Charles Lassman
SN
Susanne B. Nicholas
Susanne B. Nicholas
JH
Jeffrey F. Harper
Jeffrey F. Harper
AR
Anna E. Reeves
Anna E. Reeves
MA
Mansoor M. Ahmed
Mansoor M. Ahmed
JL
James M. Leatherman
James M. Leatherman
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1535-7163.c.6531620.v1
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
CELLS IN CULTURE
K ATPASE
TISSUE
EPITHELIAL
EMT
TARGET OF TGF
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