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The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

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Abstract

The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the αE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second αE-catenin allele. The αE-catenin gene is therefore, an invasion-suppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.

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Acknowledgements

We thank L Baeke, R Colman, A Verspeelt, K Staes and R Coquyt for technical assistance and J Roels for preparation of the illustrations. This work was supported by the Fund for Scientific Research-Flanders, The Sportvereniging tegen Kanker, The Belgian Cancer Association, The ASLK/VIVA-verzekeringen and the GOA from the Vlaamse Gemeenschap, Brussels, Belgium. FN is a Research Assistant and FVR a Research Director with the Fund for Scientific Research-Flanders.

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Authors and Affiliations

  1. Department of Radiotherapy and Nuclear Medicine, Laboratory of Experimental Cancerology, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Stefan J Vermeulen, Krist'l M Vennekens, Fransiska Malfait, Marc E Bracke & Marc M Mareel

  2. Department of Molecular Biology, Laboratory of Molecular Cell Biology, University of Gent and VIB, Ledeganckstraat 35, Gent, B-9000, Belgium

    Friedel Nollet & Frans M van Roy

  3. Laboratory of Medical Oncology, University Hospital Brussels, Laarbeeklaan 101, Jette, B-1010, Belgium

    Erik Teugels

  4. Department of Clinical Chemistry, Microbiology and Immunology, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Jan Philippé

  5. Department of Medical Genetics, University Hospital Gent, De Pintelaan 185, Gent, B-9000, Belgium

    Frank Speleman

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  1. Stefan J Vermeulen
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  2. Friedel Nollet
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Vermeulen, S., Nollet, F., Teugels, E. et al. The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. Oncogene 18, 905–915 (1999). https://doi.org/10.1038/sj.onc.1202348

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  • DOI: https://doi.org/10.1038/sj.onc.1202348

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