Insulin-like growth factor I stimulates motility in human neuroblastoma cells.
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.
Meyer
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GE
Neuroscience Program, University of Michigan, 4414 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Shelden
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Kim
B
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Feldman
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D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000502:physiology*; D020935:MAP Kinase Signaling System; D018715:Microscopy, Video; D009447:Neuroblastoma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011233:Precipitin Tests; D020033:Protein Isoforms; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases