title: Involvement of the Src-cortactin pathway in migration induced by IGF-1             and EGF in human breast cancer cells.
abstract: Cancer cells need to become motile in order to escape the primary tumor             and move to distant areas to form metastasis. They move as single cells or as             a group, following different stimuli, including growth factors. Among them, insulin-like             growth factor‑1 (IGF-1) and epidermal growth factor (EGF) and their receptors             have been implicated in the development and progression of human breast carcinoma.             In this report, we provide evidence that the tyrosine kinase Src is responsible             for migration promoted by both IGF-1 and EGF in MDA-MB-231 and MCF7 cells, although             with a different effect. Moreover, both IGF-1 and EGF induce reorganization of             actin cytoskeleton in lamellipodia and membrane ruffles in a time- and Src-dependent             manner. Furthermore, we analyzed the tyrosine phosphorylation status of the actin-binding             protein cortactin upon growth factor stimulation, showing that even the activation             of cortactin is time- and Src-dependent. In addition, immunofluorescence analysis             with anti-paxillin antibody reveals that, after treatment with growth factors,             tyrosine phosphorylated cortactin is localized on the plasma membrane in correspondence             of focal adhesions. Collectively, our findings suggest a crucial role for Src-mediated             activation of cortactin in cell migration, reorganization of actin cytoskeleton             and phosphotyrosine cortactin localization to the focal adhesions in human breast             cancer cell lines upon both IGF-1 and EGF stimulation.
authors.affiliation: Department of Radiology, Oncology and Human Pathology, Division                     of Oncology B, Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mezi
authors.forename: Laura
authors.initials: L
authors.lastname: Todi
authors.forename: Errico
authors.initials: E
authors.lastname: Orsi
authors.forename: Antonio
authors.initials: A
authors.lastname: Angeloni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancini
mesh_terms: D000199:Actins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D051356:Cortactin / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D061986:MCF-7 Cells; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D051356:Cortactin; D014443:Tyrosine; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D019061:src-Family Kinases