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First published online October 10, 2007

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Apoptosis resistance – the third dimension

Apoptosis is essential for tissue development and homeostasis. When it goes wrong, one consequence can be cancer. We know little about how apoptosis is regulated in tissues, however. Why, for example, are mammary epithelial cells (MECs) growing as acini (3D tissue-like structures) in reconstituted basement membrane resistant to apoptosis? On p. 3700 Valerie Weaver and colleagues suggest that such cells resist apoptosis because 64 integrins on their surface activate the GTPase Rac, which stimulates p21-activated kinase 1 (Pak1) and consequently the anti-apoptotic signal transducer NF-B. They have examined resistance to apoptosis in non-malignant human MECs growing on or in reconstituted basement membrane (i.e. in 2D or 3D cultures, respectively). Among their results, the authors show that inhibition of Pak1 makes mammary acini sensitive to apoptosis; this effect is reversed by expression of NF-B. Conversely, they report, acini expressing elevated levels of Pak1 can activate NF-B and resist apoptotic stimuli even in the absence of activated Rac. These data emphasize the importance of the basement membrane in the regulation of apoptosis and, in addition, identify Pak1 inhibitors as potential anti-tumour agents.

Related articles in JCS:

64 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-B-dependent resistance to apoptosis in 3D mammary acini

Julie C. Friedland, Johnathon N. Lakins, Marcelo G. Kazanietz, Jonathan Chernoff, David Boettiger, and Valerie M. Weaver
JCS 2007 120: 3700-3712. [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