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The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the control of cell-cell junction and induces dissociation and dispersion of MDCK cells

Oncogene volume 21, pages 1477–1484 (2002)Cite this article

Abstract

Hepatocyte growth factor (HGF) induces the breakdown of cell junction and the dispersion of colonies of epithelial cells, providing a model system for the investigation of the molecular mechanisms of one of the important aspects of tumorogenesis. We have previously reported that the SH2-domain-containing inositol 5′phosphatase (SHIP)-1 binds to c-Met, and potentiated HGF-mediated branching tubulogenesis. In this study, we describe the establishment of MDCK cell lines which express MycHis-tagged SHIP-1 at different levels. Expression of SHIP-1 in MDCK cells at a high level resulted in cell morphology characteristic of an epithelial-mesenchymal like transition; cells lost cortical actin, developed actin stress fibers and gained spontaneous motility without treatment of HGF. When the level of MycHis-tagged SHIP-expression was relatively low, transfectants partially lost cortical actin and phalloidin stained puncta appeared at cell–cell junctions even in the absence of HGF. The treatment of MAP kinase inhibitor, PD98059, did not influence SHIP-1 mediated alteration of adherens-junction of MDCK cells, while, phosphatidylinositol 3 (PI 3)- kinase inhibitor, LY294002, drastically reduced SHIP-1 mediated phenotype. Furthermore, expression of a mutant SHIP-1 lacking catalytic activity in MDCK cells did not alter the cortical actin distribution and HGF-mediated MAP and Akt kinase-phosphorylation, but suppressed HGF induced cell dispersion, suggesting that phosphatase activity is important for cytoskeleton rearrangement and cell dispersion.

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Acknowledgements

We thank Karsten Heidrich (MHH) for technical assistance, Larry Rohrschneider (Fred Hutchinson Cancer center, Seattle) for providing the SHIP cDNA, C Bruce Boschek for critically reading the manuscript. This research was supported by the Deutsche Forschungsgemeinschaft (Ta-111/8/-1), SFB566 (B2) and HiLF program to A Mancini.

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  1. Institut für Biochemie, OE 4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, D-30623, Germany

    Annalisa Mancini, Alexandra Koch, Regina Wilms & Teruko Tamura

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  1. Annalisa Mancini
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  2. Alexandra Koch
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Correspondence to Teruko Tamura.

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Mancini, A., Koch, A., Wilms, R. et al. The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the control of cell-cell junction and induces dissociation and dispersion of MDCK cells. Oncogene 21, 1477–1484 (2002). https://doi.org/10.1038/sj.onc.1205224

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