Nav: Home

Blocking two enzymes could make cancer cells mortal

May 16, 2018

Before cell division, the long strings of the cell's DNA are wrapped tightly into the structures we know as chromosomes. This protects the cell's genetic material from physical and chemical damage.

The ends of chromosomes are called telomeres. These are specialized structures that have to be replicated with each cell division cycle. But the complete replication of telomeres up to the very ends of chromosomes also requires specialized mechanisms, and these are limited. Telomeres are also very sensitive to oxidative damage, which affects their ability to replicate.

Because of this, telomeres shrink over time, limiting the lifespan of cells. Telomere shortening is essentially the cause of cell aging.

Now, Joachim Lingner and Wareed Ahmed at EPFL have discovered two antioxidant enzymes that work together to prevent oxidation of telomeric DNA at chromosome ends. The scientists disrupted both the enzymes, called PRDX1 and MTH1, in cancer cells, and found that the cells' telomeres shrunk with every round of cell division, eventually disappearing altogether.

One of the promising targets in cancer therapy is the enzyme telomerase. Normally, telomerase prevents telomeres from shortening in germ and stem cells, which helps with development. But telomerase is also highly active in cancer cells, keeping their telomeres intact and making the cells virtually immortal. The new work shows that disrupting PRDX1 and MTH1 prevents telomerase from counteracting telomere shortening.

So far, attempts to efficiently block telomerase in cancer have not been fruitful in the clinic. The discovery of the co-operating enzymes opens up a new opportunity to indirectly block telomerase. "Instead of inhibiting the enzyme itself, we target its substrate - the chromosome end - making it un-extendable by telomerase," says Lingner.
-end-
Funding
  • Swiss National Science Foundation (SNSF)

  • NCCR RNA & Disease

  • Swiss Cancer League

  • EPFL

Reference

Wareed Ahmed, Joachim Lingner. PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerase. Genes & Development 17 May 2018. DOI: 10.1101/gad.313460.118

Ecole Polytechnique Fédérale de Lausanne

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
More Stem Cells News and Stem Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...