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p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion

Oncogene volume 22, pages 4841–4850 (2003)Cite this article

Abstract

Transforming growth factor beta (TGFβ) regulates cell adhesion, proliferation, and differentiation in a variety of cells. Smad proteins are receptor-activated transcription factors that translocate to the nucleus in response to TGFβ. We demonstrate here that TGFβ increases cell adhesion in metastatic PC3-M prostate cancer cells. TGFβ treatment of PC3-M cells leads to nuclear translocation of R-Smad proteins. We show that Smad proteins are necessary, but not sufficient, for TGFβ-mediated cell adhesion. After showing that TGFβ upregulated p38 MAP kinase activity in PC3-M cells, we show that inhibition of p38 MAP kinase partially blocked TGFβ-mediated increase in cell adhesion, as well as nuclear translocation of Smad3. Finally, we show that Smad3 is phosphorylated by p38 MAP kinase in vitro. These findings implicate crosstalk between the MAP kinase and Smad signaling pathways in TGFβ's regulation of cell adhesion in human prostate cells. This represents a mechanism by which the pleiotropic effects of TGFβ may be channeled to modulate cell adhesion.

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Acknowledgements

This work was supported by a Prostate SPORE grant from the National Cancer Institute (CA90386) and by grants CA77816 and CA9407 (to LCP). SAH is a Drug Discovery Program Postdoctoral Scholar (T32 AG00260).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine Northwestern University Medical School and the Robert H Lurie Cancer Center of Northwestern University, Olson 8524, 710 N. Fairbanks, Chicago, 60611-3008, IL, USA

    Steven A Hayes, Xiaoke Huang, Suman Kambhampati, Leonidas C Platanias & Raymond C Bergan

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  1. Steven A Hayes
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  2. Xiaoke Huang
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Correspondence to Raymond C Bergan.

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Hayes, S., Huang, X., Kambhampati, S. et al. p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion. Oncogene 22, 4841–4850 (2003). https://doi.org/10.1038/sj.onc.1206730

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