Abstract
Epithelial-mesenchymal transition (EMT) is an important process during development and oncogenesis by which epithelial cells acquire fibroblast-like properties and show reduced intercellular adhesion and increased motility. Squamous cell carcinoma lines engineered to express constitutively active Akt underwent EMT, characterized by down-regulation of the epithelial markers desmoplakin, E-cadherin, and beta-catenin and up-regulation of the mesenchymal marker vimentin. The cells lost epithelial cell morphology and acquired fibroblast-like properties. Additionally, E-cadherin was down-regulated transcriptionally. The cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated surfaces, and increased invasiveness in animals. AKT is activated in many human carcinomas, and the AKT-driven EMT may confer the motility required for tissue invasion and metastasis. These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cadherins / biosynthesis
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Cadherins / genetics
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Cadherins / metabolism
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Carcinoma, Squamous Cell / enzymology*
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Carcinoma, Squamous Cell / pathology*
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Cell Adhesion / physiology
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Cell Division / physiology
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Cell Movement / physiology*
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Down-Regulation
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Enzyme Activation
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Epithelial Cells / enzymology
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Epithelial Cells / pathology
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Gene Expression Regulation, Neoplastic
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Humans
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Mesoderm / enzymology
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Mesoderm / pathology
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Neoplasm Invasiveness
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Snail Family Transcription Factors
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Subcellular Fractions / metabolism
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Trans-Activators / biosynthesis
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Trans-Activators / metabolism
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Tumor Cells, Cultured
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Up-Regulation
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Vimentin / biosynthesis
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beta Catenin
Substances
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CTNNB1 protein, human
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Cadherins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Snail Family Transcription Factors
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Trans-Activators
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Transcription Factors
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Vimentin
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beta Catenin
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt