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Mechanisms of regulation of cell adhesion and motility by insulin receptor substrate-1 in prostate cancer cells

Oncogene volume 20, pages 490–500 (2001)Cite this article

Abstract

LNCaP cells are human prostatic cancer cells that have a frame-shift mutation of the tumor suppressor gene PTEN and do not express the insulin receptor substrate-1 (IRS-1), a major substrate of the type 1 insulin-like growth factor receptor (IGF-IR). Ectopic expression of IRS-1 in LNCaP cells increases cell adhesion and decreases cell motility by an IGF-I-independent mechanism. We show now that these effects of IRS-1 are accompanied by serine phosphorylation of IRS-1 and are inhibited by inhibitors of phosphatidylinositol 3-kinase (PI3K). We have confirmed the requirement for PI3K activity and serine phosphorylation by the use of IRS-1 mutants, expressed in LNCaP cells. Serine phosphorylation inhibits IGF-I-induced tyrosyl phosphorylation of IRS-1, which is restored by the expression of wild-type PTEN or by inhibition of PI3K activity. Finally, IRS-1 in LNCaP cells co-immunoprecipitates with integrin α 5 β 1, and the association is again IGF-I-independent. We conclude that in LNCaP cells, IRS-1 is serine phosphorylated by PI3K, generating effects that are different, and even opposite, from those generated by IGF-I.

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Acknowledgements

This work is supported by grants CA 56309 and AG 16291 from the National Institutes of Health. K Reiss is a recipient of grant DHHS PO-1 NS 36466.

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  1. Krzysztof Reiss & Jin-Ying Wang

    Present address: Temple University, College of Science and Technology, Center for Neurovirology and Cancer Biology, 205 Biology Life Science Building, 1900 North 12th Street, Philadelphia, PA 19122, USA

Authors and Affiliations

  1. Kimmel Cancer Center, Thomas Jefferson University, 624 Biology Life Science Building, 233 South 10th Street, Philadelphia, PA 19107, Pennsylvania, USA

    Krzysztof Reiss, Jin-Ying Wang, Gaetano Romano, Xiao Tu, Francesca Peruzzi & Renato Baserga

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Reiss, K., Wang, JY., Romano, G. et al. Mechanisms of regulation of cell adhesion and motility by insulin receptor substrate-1 in prostate cancer cells. Oncogene 20, 490–500 (2001). https://doi.org/10.1038/sj.onc.1204112

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