Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells

Mezi,Silvia; Todi,Laura; Orsi,Errico; Angeloni,Antonio; Mancini,Patrizia

doi:10.3892/ijo.2012.1642

Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells

Authors:
- Silvia Mezi
- Laura Todi
- Errico Orsi
- Antonio Angeloni
- Patrizia Mancini
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Affiliations: Department of Radiology, Oncology and Human Pathology, Division of Oncology B, Sapienza University of Rome, Rome, Italy, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy, Department of Surgical Science, Division of DEA, Sapienza University of Rome, Rome, Italy, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Published online on: September 26, 2012 https://doi.org/10.3892/ijo.2012.1642
Pages: 2128-2138

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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.

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