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Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

Oncogene volume 26, pages 2381–2385 (2007)Cite this article

Abstract

Pancreatic cancer is a devastating disease with poor prognosis. Production of large quantities of extracellular matrix and early metastasis are characteristics of this disease. One important step in the development of various cancers is the loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell–cell adhesion. It has been shown that collagen type I promotes downregulation of E-cadherin expression, which correlates with enhanced cell migration and invasiveness. In this context, we elucidated the role of Smad-interacting protein 1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene expression. We demonstrate that SIP1 upregulation shows an inverse relationship with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1 expression can be induced by exposure to collagen type I in a src-dependent manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein levels. Taken together, these results suggest that SIP1 is involved in the progression of pancreatic cancer and plays a role in mediating signal transduction from collagen type I to downregulate E-cadherin expression.

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Acknowledgements

We thank Dr Walter Birchmeier (MDC, Berlin, Germany) for the gift of the pCat-Ecad178 plasmid. This work was funded by the DFG, SFB 518.

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  1. Y Imamichi and A König: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany

    Y Imamichi, A König & A Menke

  2. Department of Gastroenterology/Endocrinology and Metabolism, University Hospital Giessen and Marburg, Marburg, Germany

    T Gress

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  1. Y Imamichi
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  2. A König
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  3. T Gress
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  4. A Menke
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Correspondence to Y Imamichi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Imamichi, Y., König, A., Gress, T. et al. Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer. Oncogene 26, 2381–2385 (2007). https://doi.org/10.1038/sj.onc.1210012

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