E-cadherin surface levels in epithelial growth factor-stimulated cells depend on adherens junction protein shrew-1.
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.
Gross
Julia Christina
JC
Institute for Cell Biology and Neuroscience, Johann Wolfgang Goethe University of Frankfurt, 60323 Frankfurt, Germany.
Schreiner
Alexander
A
Engels
Knut
K
Starzinski-Powitz
Anna
A
D022005:Adherens Junctions / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D042361:Mammary Glands, Human / Q000378:metabolism; D018613:Microscopy, Confocal; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
D015820:Cadherins; D015815:Cell Adhesion Molecules; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D049452:Green Fluorescent Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019061:src-Family Kinases; C483313:AJAP1 protein, human