New Organelle Found That Helps Prevent
Cancer
October 18, 2019 -- Scientists at the [University
of Virginia] School of Medicine have discovered a strange new organelle inside
our cells that helps to prevent cancer by ensuring that genetic material is
sorted correctly as cells divide.
The researchers have connected problems
with the organelle to a subset of breast cancer tumors that make lots of
mistakes when segregating chromosomes. Excitingly, they found their analysis
offered a new way for doctors to sort patient tumors as they choose therapies.
They hope these insights will allow doctors to better personalize treatments to
best benefit patients – sparing up to 40 percent of patients with breast
cancer, for example, a taxing treatment that won’t be effective.
“Some percentage of women get
chemotherapy drugs for breast cancer that are not very effective. They are
poisoned, in pain and their hair falls out, so if it isn’t curing their
disease, then that’s tragic,” said researcher P. Todd Stukenberg, PhD, of UVA’s
Department of Biochemistry and Molecular Genetics and the UVA Cancer Center. “One
of our goals is to develop new tests to determine whether a patient will
respond to a chemotherapeutic treatment, so they can find an effective
treatment right away.”
The
Disappearing Organelle
The organelle Stukenberg and his team
have discovered is essential but ephemeral. It forms only when needed to ensure
chromosomes are sorted correctly and disappears when its work is done. That’s
one reason scientists haven’t discovered it before now. Another reason is its
mind-bending nature: Stukenberg likens it to a droplet of liquid that condenses
within other liquid. “That was the big wow moment, when I saw that on the
microscope,” he said.
These droplets act as mixing bowls,
concentrating certain cellular ingredients to allow biochemical reactions to
occur in a specific location. “What’s exciting is that cells have this new
organelle and certain things will be recruited into it and other things will be
excluded,” Stukenberg said. “The cells enrich things inside the droplet and,
all of a sudden, new biochemical reactions appear only in that location. It’s
amazing.”
It’s tempting to think of the droplet
like oil in water, but it’s really the opposite of that. Oil is hydrophobic –
it repels water. This new organelle, however, is more sophisticated. “It’s more
of a gel, where cellular components can still go in and out but it contains
binding sites that concentrate a small set of the cells contents,” Stukenberg
explained. “Our data suggests this concentration of proteins is really
important. I can get complex biochemical reactions to occur inside a droplet
that I’ve been failing to reconstitute in a test tube for years. This is the
secret sauce I’ve been missing.”
While it’s been known for about eight
years that cells make such droplets for other processes, but it was unknown
that they make them on chromosomes during cell division. Stukenberg believes
these droplets are very common and more important than previously realized. “I
think this is a general paradigm,” he said. “Cells are using these
non-membranous organelles to regulate much of their work.”
Better Cancer
Treatments
In addition to helping us understand
mitosis – how cells divide – Stukenberg’s new discovery also sheds light on
cancer and how it occurs. The organelle’s main function is to fix mistakes in
tiny “microtubules” that pull apart chromosomes when cells are dividing. That
ensures each cell winds up with the correct genetic material. In cancer,
though, this repair process is defective, which can drive cancer cells to get
more aggressive.
He has also developed tests to measure
the amount of chromosome mis-segregation in tumors, and he hopes that this
might allow doctors to pick the proper treatment to give cancer patients. “We
have a way to identify the tumors where the cells are mis-segregating
chromosomes at a higher rate,” he said. “My hope is to identify the patients
where treatments such as paclitaxel are going to the most effective.”
Having looked at breast cancer already,
he next plans to examine the strange organelle’s role in colorectal cancer.
Findings
Published
Stukenberg and his colleagues have
described their latest discovery in the scientific journal Nature Cell Biology.
The research team consisted of Prasad Trivedi, Francesco Palomba, Ewa
Niedzialkowska, Michelle A. Digman, Enrico Gratton and Stukenberg.
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