Research by scientists at Cancer Research UK's London Research
Institute (LRI; now part of the Francis Crick Institute) offers a
possible explanation for how human tissues such as skin grow in
response to stretching forces.
Dr Barry Thompson's group at LRI found a new function for the
Spectrin cytoskeleton - the lesser known of three types of
cytoskeleton. Cytoskeletons are the networks in cells that provide
structure, shape and help with cell movement. Dr Thompson's group
found that the Spectrin cytoskeleton also plays a role in sensing
forces and regulating tissue growth.
It was already known that Spectrin proteins associate closely
with the inside surface of a cell's plasma membrane (which
separates the contents of the cell from the outside environment).
It was also known that Spectrins can form spring-like networks that
can stretch under force. The team has now shown that cells can use
the Spectrin cytoskeleton to regulate cell multiplication and
growth in response to outside forces.
The scientists removed the genes for Spectrin in the fruit fly
Drosophila and looked at how this affected tissue growth. They also
used a technique called RNA interference to turn off the Spectrin
genes in Drosophila and human epithelial
cells.
Their results revealed that, in normal cells under normal
conditions, Spectrins keep cell growth levels low through a
molecular pathway known as Hippo. However when there is tension
exerted on the cells, Spectrins no longer activate the Hippo
pathway and cells begin to grow and divide.
Dr Thompson said: "Our findings suggest a new way in which cells
can sense external forces applied to them, and can then use this
information to regulate their behaviour.
"The growth of human tissues such as skin is known to be
stimulated by stretching forces, so our results suggest a possible
mechanism to explain how this works."
The paper, The Spectrin cytoskeleton regulates the Hippo signalling
pathway, is published inThe EMBO
Journal.