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FXYD5 (dysadherin) may mediate metastatic progression through regulation of the β-Na + -K + -ATPase subunit in the 4T1 mouse breast cancer model.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2017 Jul 01; Vol. 313 (1), pp. C108-C117. Date of Electronic Publication: 2017 May 17. - Publication Year :
- 2017
-
Abstract
- FXYD5 is a Na <superscript>+</superscript> -K <superscript>+</superscript> -ATPase regulator, expressed in a variety of normal epithelia. In parallel, it has been found to be associated with several types of cancer and effect lethal outcome by promoting metastasis. However, the molecular mechanism underlying FXYD5 mediated invasion has not yet been identified. In this study, using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA significantly inhibited lung cancer metastasis, without having a substantial effect on primary tumor growth. Our study reveals that FXYD5 participates in multiple stages of metastatic development and exhibits more than one mode of E-cadherin regulation. We provide the first evidence that FXYD5-related morphological changes are mediated through its interaction with Na <superscript>+</superscript> -K <superscript>+</superscript> -ATPase. Experiments in cultured 4T1 cells have indicated that FXYD5 expression may downregulate the β1 isoform of the pump. This behavior could have implications on both transcellular interactions and intracellular events. Further studies suggest that differential localization of the adaptor protein Annexin A2 in FXYD5-expressing cells may correlate with matrix metalloproteinase 9 secretion and adhesion changes in 4T1 wild-type cells.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Animals
Annexin A2 genetics
Annexin A2 metabolism
Cadherins genetics
Cadherins metabolism
Cell Adhesion
Cell Line, Tumor
Cell Movement
Disease Models, Animal
Female
Ion Channels
Lung Neoplasms metabolism
Lung Neoplasms secondary
Mammary Glands, Animal metabolism
Mammary Glands, Animal pathology
Mammary Neoplasms, Experimental metabolism
Mammary Neoplasms, Experimental pathology
Matrix Metalloproteinase 9 genetics
Matrix Metalloproteinase 9 metabolism
Membrane Proteins antagonists & inhibitors
Membrane Proteins metabolism
Mice
Mice, Inbred BALB C
Microfilament Proteins
Neoplasms, Adipose Tissue metabolism
Neoplasms, Adipose Tissue pathology
Protein Subunits genetics
Protein Subunits metabolism
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Sodium-Potassium-Exchanging ATPase metabolism
Gene Expression Regulation, Neoplastic
Lung Neoplasms genetics
Mammary Neoplasms, Experimental genetics
Membrane Proteins genetics
Neoplasms, Adipose Tissue genetics
Sodium-Potassium-Exchanging ATPase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1563
- Volume :
- 313
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 28515087
- Full Text :
- https://doi.org/10.1152/ajpcell.00206.2016