Abstract
Gain- and loss-of-function studies indicate that the adherens junction protein shrew-1 acts as a novel modulator of E-cadherin internalization induced by epithelial growth factor (EGF) or E-cadherin function-blocking antibody during epithelial cell dynamics. Knocking down shrew-1 in MCF-7 carcinoma cells preserves E-cadherin surface levels upon EGF stimulation. Overexpression of shrew-1 leads to preformation of an E-cadherin/EGF receptor (EGFR) HER2/src-kinase/shrew-1 signaling complex and accelerated E-cadherin internalization. Shrew-1 is not sufficient to stimulate E-cadherin internalization, but facilitates the actions of EGFR and thus may promote malignant progression in breast cancer cells with constitutive EGFR stimulation by reducing surface E-cadherin expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adherens Junctions / drug effects*
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Adherens Junctions / metabolism
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cadherins / metabolism*
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Line, Tumor
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Cell Movement / drug effects
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Endocytosis / drug effects
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Epidermal Growth Factor / pharmacology*
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ErbB Receptors / metabolism
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Fluorescent Antibody Technique
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Immunoblotting
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Mammary Glands, Human / metabolism
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Microscopy, Confocal
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RNA Interference
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Receptor, ErbB-2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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src-Family Kinases / metabolism
Substances
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AJAP1 protein, human
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Cadherins
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Cell Adhesion Molecules
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Green Fluorescent Proteins
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Epidermal Growth Factor
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ErbB Receptors
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Receptor, ErbB-2
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src-Family Kinases