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First published online July 2, 2007

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Polar route to apoptosis

Epithelial cells are normally polarized but lose their polarity during carcinogenesis. They also begin to divide uncontrollably and become resistant to apoptosis. Could these three hallmarks of cancer be linked by a common molecular mechanism? On p. 2309, Keith Mostov and co-workers reveal that they could be by showing that the polarity protein partitioning defective 6 (PAR6) is involved in epithelial cell survival. A domain in the N-terminus of PAR6 interacts with and activates atypical protein kinase C (aPKC). The authors report that expression of an N-terminally deleted PAR6 mutant during the epithelial morphogenesis of Madin-Darby canine kidney cells in 3D cultures not only partly disrupts their polarity but also greatly increases caspase-dependent cell death by downregulating aPKC activity. Similarly, knocking down aPKC in wild-type cells by RNAi promotes apoptosis. Mostov and co-workers also show that inactivation of aPKC causes hyperactivation of its substrate glycogen synthase kinase 3 (GSK-3), and it is this that stimulates apoptosis. Thus, they conclude, a PAR6–aPKC–GSK-3 pathway links cell polarity and death of epithelial cells.

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Related articles in JCS:

Polarity proteins PAR6 and aPKC regulate cell death through GSK-3 in 3D epithelial morphogenesis

Minji Kim, Anirban Datta, Paul Brakeman, Wei Yu, and Keith E. Mostov
JCS 2007 120: 2309-2317. [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?