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Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
by
Hakomori, Sen-itiroh
, Handa, Kazuko
, Guan, Feng
in
Animals
/ Biological Sciences
/ bladder
/ breast neoplasms
/ Cadherins
/ Cancer
/ Cell adhesion
/ Cell Line
/ Cell lines
/ Cell motility
/ Cell Movement
/ Cells
/ Cultured cells
/ embryogenesis
/ Embryonic growth stage
/ Embryonic stem cells
/ Enzyme Inhibitors - pharmacology
/ Epithelial cells
/ Epithelial Cells - cytology
/ Epithelial Cells - drug effects
/ Epithelial Cells - physiology
/ epithelium
/ fibronectins
/ G(M2) Ganglioside - pharmacology
/ Gangliosides
/ Gangliosides - pharmacology
/ Genotype & phenotype
/ Glucosyltransferases - antagonists & inhibitors
/ glycosphingolipids
/ Glycosphingolipids - metabolism
/ Glycosphingolipids - physiology
/ Humans
/ mammary glands
/ Mesenchymal stem cells
/ Mesoderm - cytology
/ Mesoderm - drug effects
/ Mesoderm - physiology
/ Mice
/ Molecules
/ phenotype
/ Propanolamines - pharmacology
/ Pyrrolidines - pharmacology
/ Rodents
/ Studies
/ transforming growth factor beta
/ Transforming Growth Factor beta - pharmacology
/ vimentin
2009
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Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
by
Hakomori, Sen-itiroh
, Handa, Kazuko
, Guan, Feng
in
Animals
/ Biological Sciences
/ bladder
/ breast neoplasms
/ Cadherins
/ Cancer
/ Cell adhesion
/ Cell Line
/ Cell lines
/ Cell motility
/ Cell Movement
/ Cells
/ Cultured cells
/ embryogenesis
/ Embryonic growth stage
/ Embryonic stem cells
/ Enzyme Inhibitors - pharmacology
/ Epithelial cells
/ Epithelial Cells - cytology
/ Epithelial Cells - drug effects
/ Epithelial Cells - physiology
/ epithelium
/ fibronectins
/ G(M2) Ganglioside - pharmacology
/ Gangliosides
/ Gangliosides - pharmacology
/ Genotype & phenotype
/ Glucosyltransferases - antagonists & inhibitors
/ glycosphingolipids
/ Glycosphingolipids - metabolism
/ Glycosphingolipids - physiology
/ Humans
/ mammary glands
/ Mesenchymal stem cells
/ Mesoderm - cytology
/ Mesoderm - drug effects
/ Mesoderm - physiology
/ Mice
/ Molecules
/ phenotype
/ Propanolamines - pharmacology
/ Pyrrolidines - pharmacology
/ Rodents
/ Studies
/ transforming growth factor beta
/ Transforming Growth Factor beta - pharmacology
/ vimentin
2009
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Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
by
Hakomori, Sen-itiroh
, Handa, Kazuko
, Guan, Feng
in
Animals
/ Biological Sciences
/ bladder
/ breast neoplasms
/ Cadherins
/ Cancer
/ Cell adhesion
/ Cell Line
/ Cell lines
/ Cell motility
/ Cell Movement
/ Cells
/ Cultured cells
/ embryogenesis
/ Embryonic growth stage
/ Embryonic stem cells
/ Enzyme Inhibitors - pharmacology
/ Epithelial cells
/ Epithelial Cells - cytology
/ Epithelial Cells - drug effects
/ Epithelial Cells - physiology
/ epithelium
/ fibronectins
/ G(M2) Ganglioside - pharmacology
/ Gangliosides
/ Gangliosides - pharmacology
/ Genotype & phenotype
/ Glucosyltransferases - antagonists & inhibitors
/ glycosphingolipids
/ Glycosphingolipids - metabolism
/ Glycosphingolipids - physiology
/ Humans
/ mammary glands
/ Mesenchymal stem cells
/ Mesoderm - cytology
/ Mesoderm - drug effects
/ Mesoderm - physiology
/ Mice
/ Molecules
/ phenotype
/ Propanolamines - pharmacology
/ Pyrrolidines - pharmacology
/ Rodents
/ Studies
/ transforming growth factor beta
/ Transforming Growth Factor beta - pharmacology
/ vimentin
2009
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Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
Journal Article
Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
2009
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Overview
Epithelial-to-mesenchymal cell transition (EMT) is a basic process in embryonic development and cancer progression. The present study demonstrates involvement of glycosphingolipids (GSLs) in the EMT process by using normal murine mammary gland NMuMG, human normal bladder HCV29, and human mammary carcinoma MCF7 cells. Treatment of these cells with D-threo-1-(3',4'-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4), the glucosylceramide (GlcCer) synthase inhibitor, which depletes all GSLs derived from GlcCer, (i) down-regulated expression of a major epithelial cell marker, E-cadherin; (ii) up-regulated expression of mesenchymal cell markers vimentin, fibronectin, and N-cadherin; (iii) enhanced haptotactic cell motility; and (iv) converted epithelial to fibroblastic morphology. These changes also were induced in these cell lines with TGF-β, which is a well-documented EMT inducer. A close association between specific GSL changes and EMT processes induced by EtDO-P4 or TGF-β is indicated by the following findings: (i) The enhanced cell motility of EtDO-P4-treated cells was abrogated by exogenous addition of GM2 or Gg4, but not GM1 or GM3, in all 3 cell lines. (ii) TGF-β treatment caused changes in the GSL composition of cells. Notably, Gg4 or GM2 was depleted or reduced in NMuMG, and GM2 was reduced in HCV29. (iii) Exogenous addition of Gg4 inhibited TGF-β-induced changes of morphology, motility, and levels of epithelial and mesenchymal markers. These observations indicate that specific GSLs play key roles in defining phenotypes associated with EMT and its reverse process (i.e., mesenchymal-to-epithelial transition).
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ bladder
/ Cancer
/ Cells
/ Enzyme Inhibitors - pharmacology
/ Epithelial Cells - drug effects
/ Epithelial Cells - physiology
/ G(M2) Ganglioside - pharmacology
/ Glucosyltransferases - antagonists & inhibitors
/ Glycosphingolipids - metabolism
/ Glycosphingolipids - physiology
/ Humans
/ Mice
/ Propanolamines - pharmacology
/ Rodents
/ Studies
/ transforming growth factor beta
/ Transforming Growth Factor beta - pharmacology
/ vimentin
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