Abstract
The endocannabinoid system regulates cell proliferation and migration in human breast cancer cells. In this study, we showed that a metabolically stable analog of anandamide, 2-methyl-2'-F-anandamide (Met-F-AEA), inhibited the RHOA activity and caused a RHOA delocalization from the cell membrane to cytosol determining a decrease in actin stress fibers. Overexpression of a dominant negative of RHOA activity and treatment of these cells with a RHO-associated protein kinase (ROCK) inhibitor, Y 27632, mimicked Met-F-AEA effects on actin organization and cell migration. We suggest that the inhibitory effect of Met-F-AEA on tumor cell migration could be related to RHOA-ROCK-dependent signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Amides / pharmacology
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Arachidonic Acids / pharmacology*
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Blotting, Western
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Cannabinoids / pharmacology
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Cell Membrane / enzymology
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Cell Movement / drug effects*
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Cytoskeleton / metabolism
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Cytosol / enzymology
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Female
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Fluorescent Antibody Technique
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Humans
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Mevalonic Acid / pharmacology
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Neoplasm Invasiveness
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Pyridines / pharmacology
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Signal Transduction / drug effects*
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rho-Associated Kinases / metabolism*
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rhoA GTP-Binding Protein / metabolism*
Substances
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2-methylarachidonyl-2'-fluoroethylamide
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Actins
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Amides
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Arachidonic Acids
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Cannabinoids
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Pyridines
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Y 27632
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rho-Associated Kinases
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rhoA GTP-Binding Protein
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Mevalonic Acid