Abstract
Motility is an important process that contributes to cancer cell spread. Growth factors are key regulators of motility in many cell types. Insulin-like growth factor I (IGF-I) causes SH-SY5Y human neuroblastoma cells to undergo dynamic morphological changes, leading to the extension of lamellipodia. IGF-I stimulated lamellipodia extension requires signaling through both phosphatidylinositol 3-kinase (PI3-K) and MAP kinase pathways. IGF-I, over a period of hours, stimulates SH-SY5Y and SHEP neuroblastoma cells to become more motile. While SH-SY5Y and SHEP cells use different insulin receptor substrate (IRS) isoforms to transduce signals from the IGF-I receptor, IGF-I has the same relative effect on the motility of both cell lines. Blocking the PI3-K and MAP kinase pathways attenuates the ability of IGF-I to increase motility. Overexpression of PTEN also attenuates IGF-I mediated motility. These results delineate some of the proximal events in the signaling mechanism utilized by IGF-I to stimulate cell motility.
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Acknowledgements
The authors acknowledge Yutein Chung for technical assistance, Kathleen Ignatowski and Cynthia van Golen for preparation of the SHEP-PTEN transfectants, and Judith Boldt for secretarial assistance. This work was supported by NIH RO1 NS38849 (EL Feldman) and 5T32 GM07863 and 5T32 CA09676 (GE Meyer).
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Meyer, G., Shelden, E., Kim, B. et al. Insulin-like growth factor I stimulates motility in human neuroblastoma cells. Oncogene 20, 7542–7550 (2001). https://doi.org/10.1038/sj.onc.1204927
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DOI: https://doi.org/10.1038/sj.onc.1204927
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