Published online
doi:10.1083/jcb.1781iti2
The Journal of Cell Biology, Vol. 178, No. 1, 3b-
The Rockefeller University Press, 0021-9525 $30.00
© Leslie
p53 hits the brakes
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A p53-expressing fibroblast (top) is outrun by a fast crawler lacking p53 (bottom).
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Crawling cells shift into high gear after they lose the tumor suppressor protein p53, as Gadea et al. report on page 23. The work reveals that the same flaw that allows cancer cells to divide uncontrollably also increases their mobility.
Most cancer cells sport faulty versions of p53, which normally halts the cell cycle or triggers apoptosis in response to DNA damage. The researchers and other groups had previously shown that deleting p53 gets cells moving in two-dimensional cultures. Gadea et al. tested for the same effect in more realistic, three-dimensional cultures.
The researchers found that crawling mouse embryonic fibroblasts came in two varieties. If they carried working p53, the cells were elongated and sluggish. But if p53 was absent, they were rounder and slithered six times faster. This speedier movement required RhoA GTPase and its downstream enforcer, ROCK.
Inactivating p53 in melanoma cells that normally carry a functional version of the protein increases their invasiveness, confirming that p53 loss can accelerate the dispersion of cancer cells. The results suggest that cancer treatments that restore p53 activity bring an added benefit by reining in the rogue cells. 
Mitch Leslie
mitchleslie{at}comcast.net
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Loss of p53 promotes RhoA–ROCK-dependent cell migration and invasion in 3D matrices
- Gilles Gadea, Marion de Toledo, Christelle Anguille, and Pierre Roux
J. Cell Biol. 2007 178: 23-30.
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