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Penn researchers show nuclear stiffness keeps stem cells and cancer cells in place
Date:2/25/2014

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"Moderate decreases in lamin-A allow more cells to migrate and live," Discher said, "but, when lamin-A is too low, death dominates migration. The narrow pore becomes a torture chamber for the DNA. We were bewildered by this and analyzed hundreds of proteins for some clue, discovering that another stress response pathway is deficient when lamin-A is very low. The heat shock proteins are famous for being turned on by high temperature stress to protect DNA and the rest of the cell, and the underlying gene circuitry somehow turns off when lamin-A is made artificially low."

The researchers showed that treating cells that have normal levels of lamin-A with a drug that inhibits heat shock proteins had the same effect as reducing lamin-A levels. The findings provide a better fundamental understanding of the roles of nuclear stiffness and stress resistance and could underpin other treatments as well.

"There really were no previous studies showing that the nucleus in stem cells and cancer cells could have such a prominent role in cell trafficking," Discher said. "And, since we confirmed some of our cell culture observations by studying human tumor growth in mice, this very physical mechanism must apply to human tissue as well. Nuclear stiffness is a property that should also help keep stem cells anchored in their niche until tissue is damaged to release the cells."


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Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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