title: Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells.
abstract: Cell migration and invasion leading to metastasis is a major cause of death from endometrial cancer (EC). We have shown that the rate of EC cell migration is inversely related to the level of insulin-like growth factor protein-3 (IGFBP-3). Down-regulation of IGFBP-3 by siRNA in EC cells accelerated migration without affecting proliferation and cells displayed a more migratory phenotype, with co-localization of migration-associated markers at the leading edge of cell membranes. Opposite effects were seen with either the addition of recombinant IGFBP-3 or overexpression of IGFBP-3. Cells with mutated PTEN had the highest IGFBP-3 expression and the slowest migration rates. This study demonstrates that endogenous IGFBP-3 modulates adhesion-migration dynamics in EC cells, implying that it may be important in regulating metastasis in this disease.
authors.affiliation: Hormones & Cancer Division, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
authors.forename: Lujia
authors.initials: L
authors.lastname: Gribben
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Marsh
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human