By Christina Hernandez Sherwood | July 22, 2010, 4:00 AM PDT
The research, by Weihang Chai of the Washington State
University School of Molecular Biosciences and colleagues,
was reported in the current issue of The EMBO Journal. It was funded in part
by the National Institutes of Health
and the American Cancer Society.
I spoke with Chai this week.
How do cancer cells differ from normal cells in terms of
their mortality?
The big difference between cancer cells and normal cells
is that cancer cells can divide forever and live forever. We call this
immortality. The normal cells will divide for a number of divisions and then
stop growing. They get old and either they die or they sit there and do
nothing. They are mortal.
Cancer cells have a way to maintain their telomeres.
Their telomeres don’t get shortened. Each time the normal cells divide they
lose some telomere DNA sequences. Eventually when the telomere DNA becomes too
short, they stop growing. There are also other factors contributing to the
mortality of normal cells.
Is the immortality of cancer cells what makes them so
dangerous?
The cancer cells divide uncontrollably. Then you have
more and more cancer cells in one location of your body that can invade the
surrounding tissues and disrupt the function of the normal tissues. They form
the tumor. The cancer cells also can circulate around your body and get into
other places and form tumors in the new locations. This is in part due to the
immortality of cancer cells. They don’t die. Normal cells grow at one location
and at some point they will stop.
Talk about your work on making cancer cells “more
mortal.”
The majority of the cancer cells, about 90 percent, they
activate a molecule called telomerase. Telomerase is usually not activated in normal
cells, except for in stem cells. In cancer cells, the telomerase is active. The
function of telomerase is to add telomere DNA at the short telomeres. That’s
why cancer cells don’t lose their telomeres. In the normal cells telomerase is
off, so there is no way to maintain their telomere length. [This would suggest
that] if you kill the telomerase in cancer cells, the telomere [would gradually
shorten] and the cancer cells will die.
However, recently we have found that the telomerase
extends just one strand of DNA. The other strand should be synthesized by other
molecules, other proteins. We found the molecule that’s responsible for
synthesizing the other strand. If you block the function of this molecule, then
the telomere cannot be maintained properly, so the cell also just stops
growing.
We’re just at this stage now. We don’t know how this
whole thing works. We’re working on that and hopefully in the future we can
design a way to target this process, not directly target telomerase but target
the synthesis of the other strand. That’s another way of stopping the cancer
cell’s growth.
What’s the next step to move this research forward?
The next step will be to find out how this whole thing is
regulated. We’d like to know whether in normal cells the synthesis of the other
strand also occurs because you want to specifically target the cancer cells. If
this does exist, [we want to know] whether the same process is regulated by
different pathways in normal cells compared to cancer cells. Our ultimate goal
is to see if there are any specific targets we can inhibit in the cancer cells.
We hope so. It’s going to be a long way. That probably
will involve some other research groups, not just our group.
Image: Dr. Weihang Chai
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