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Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in intestinal epithelial cells

Oncogene volume 21, pages 2908–2913 (2002)Cite this article

Abstract

Acquisition of resistance to anoikis (detachment-induced apoptosis) is considered to be a requirement for transformed intestinal epithelial cells to invade surrounding tissues and metastasize to distant organs. Increased Src kinase activity, which is a feature of a large proportion of colorectal cancers, has been identified as one of the factors that can contribute to anoikis resistance. However, the molecular mechanism by which high levels of Src activity contribute to anoikis resistance in intestinal epithelial cells is unknown. Here we show that high Src activity confers resistance to anoikis in intestinal epithelial cells, at least in part, by inducing Bcl-xL overexpression, and that this induction is mediated by the MEK/MAPK pathway. Based on the findings reported here, and on our previous study showing that Bcl-xL plays a critical role in ras-induced resistance to anoikis, we propose that the increased Bcl-xL levels found in colorectal cancers play a significant role in the induction of resistance to anoikis during the progression of this disease.

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Acknowledgements

We thank Penny Papadakos for her assistance in the preparation of the manuscript. We also thank Dr Natalie Ahn for the dnMEK plasmid. This work has been supported by the National Cancer Institute of Canada.

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Authors and Affiliations

  1. Division of Molecular and Cell Biology, Sunnybrook and Women's College Health Science Center, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada

    Mariano Loza Coll, Kirill Rosen, Virginia Ladeda & Jorge Filmus

  2. Department of Medical Biophysics, University of Toronto, Toronto, M5G 2M9, Ontario, Canada

    Mariano Loza Coll, Kirill Rosen, Virginia Ladeda & Jorge Filmus

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  1. Mariano Loza Coll
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  2. Kirill Rosen
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Correspondence to Jorge Filmus.

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Coll, M., Rosen, K., Ladeda, V. et al. Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in intestinal epithelial cells. Oncogene 21, 2908–2913 (2002). https://doi.org/10.1038/sj.onc.1205388

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