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First published online January 24, 2007

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Putting the Wnt up radioresistance

Epithelial stem/progenitor cells are increasingly thought to play a pivotal role in malignancy and are thought to be relatively resistant to conventional cancer therapies. Now, Jeff Rosen's group (p. 468) demonstrate a role for the Wnt/β-catenin pathway – an important developmental signalling mechanism – in mammary epithelial progenitor cell proliferation, self-renewal and radioresistance. They show that the immortalised mammary epithelial cell line COMMA-D-β-geo contains a minor population of Sca⁺ progenitor-like cells that are capable of self-renewal and asymmetric division. Constitutive activation of β-catenin within these enhances their capacity for self-renewal, which is blocked by inhibition of β-catenin signalling. Furthermore, this Sca⁺ population sustains significantly less DNA damage and is resistant to clinically relevant doses of radiation. The authors go on to show that active or non-phosphorylated β-catenin levels are higher in the Sca⁺ cells and that β-catenin relocalises to the nucleus following irradiation, where it upregulates expression of the apoptosis inhibitor survivin. This study provides evidence for progenitor cell radioresistance and defines a novel role for the Wnt/β-catenin pathway in this process. Understanding the mechanisms behind radioresistance in cancer stem cells may be an important factor in improving cancer diagnosis and treatment.

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Related articles in JCS:

Wnt/-catenin mediates radiation resistance of Sca1⁺ progenitors in an immortalized mammary gland cell line

Mercy S. Chen, Wendy A. Woodward, Fariba Behbod, Sirisha Peddibhotla, Maria P. Alfaro, Thomas A. Buchholz, and Jeffrey M. Rosen
JCS 2007 120: 468-477. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?