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Density-dependent location and interactions of truncated APC and β-catenin

Oncogene volume 23, pages 1412–1419 (2004)Cite this article

Abstract

Adenomatous polyposis coli (APC) is a multifunctional tumour suppressor protein, central to development and the mature organism. It is mutated in most cases of colorectal cancer, rendering it ineffective in mediating β-catenin degradation. We show that localization of full-length APC in colon carcinoma and noncancer cell lines is independent of cell density. However, the location of truncated APC is a function of cell density and in high-density cells truncated APC is predominantly not nuclear. Although the distribution of truncated APC and β-catenin is closely linked in subconfluent SW480 cells, at high cell density they are not colocalized. We postulated that in this cell line this could be due to an increase in β-catenin bound to E-cadherin with formation of adherens junctions at high cell density. However, while in coimmunoprecipitation assays we observe an increase in binding between β-catenin and E-cadherin and a corresponding decrease in binding between β-catenin and APC at high cell density, we did not observe a strict colocalization of β-catenin and E-cadherin at the membrane of all cells.

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Acknowledgements

We thank Dr IS Näthke, University of Dundee for the kind gift of antibody to APC (M-APC). Melanie L Davies is funded through Tenovus Cancer Research Campaign grant 35141; Gwyndaf T Roberts was supported by BBSRC grant 35086. J Wakeman was supported by a Royal Society award and North West Cancer Research Fund. Thanks to Alysia Battersby, David Pryce and Ramsay McFarlane for critical reading of this manuscript.

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  1. School of Biological Sciences, University of Wales Bangor, Deiniol Road, Bangor, LL57 2UW, Gwynedd, UK

    Melanie L Davies, Gwyndaf T Roberts & Jane A Wakeman

  2. School of Biological Sciences, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK

    David G Spiller

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  1. Melanie L Davies
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  2. Gwyndaf T Roberts
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Correspondence to Jane A Wakeman.

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Davies, M., Roberts, G., Spiller, D. et al. Density-dependent location and interactions of truncated APC and β-catenin. Oncogene 23, 1412–1419 (2004). https://doi.org/10.1038/sj.onc.1207266

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