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Hungry cells forget which way is up

The distribution of F-actin (red) shifts in AMPK mutant cells deprived of food (right).

Acell modifies its polarity depending on how much energy is available, as Mirouse et al. demonstrate on page 387. The findings suggest a link between energy status and tumor suppression.

How the tumor suppressor LKB1 keeps cancer in check is not certain. The protein fires up PAR-1, which helps establish cell polarity, and the energy-sensor AMPK. When ATP is scarce, AMPK shuts down division and other energy-draining activities. A leading hypothesis is that LKB1 controls cell polarity through PAR-1 and growth through AMPK. But pinning down AMPK's functions has been difficult because vertebrates harbor multiple genes. Drosophila, however, has only one AMPK gene, and Mirouse et al. netted some mutants.

Epithelial cells from the mutant flies seemed normal when food was abundant. But energy-strapped cells began to lose their polarity. Actin distribution was altered, for example, and a protein usually confined to the basal portion of the cell crept up the sides. Famished cells also became disorganized, forming clumps that resembled tumors. To rule out the possibility that the abnormalities stemmed from ATP scarcity, the researchers tested cells with faulty mitochondria due to a mutated tenured gene. Like their academic namesakes, the cells have little energy and don't do much. But their polarity didn't change.

The results suggest that AMPK allows cells to couple their polarity and growth to food availability. LKB1 might also exert its tumor suppressing effects in part through AMPK.

Mitch Leslie

mitchleslie{at}comcast.net

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Related Article

LKB1 and AMPK maintain epithelial cell polarity under energetic stress

Vincent Mirouse, Lance L. Swick, Nevzat Kazgan, Daniel St Johnston, and Jay E. Brenman
J. Cell Biol. 2007 177: 387-392. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 916K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                            What's this?