Medical News Today: How could designer proteins thwart cancer?

Chromosomes, or DNA molecules found in cells carrying genetic material, are “bookended” by telomeres, which will prevent them from “unraveling.” Telomeres are also important in the growth and aging process of cells, but what happens when cancer “hijacks” them, and can this be prevented?
scientist looking through a microscope
Scientists have developed specialized proteins that can interfere with cancer’s growth strategy at a molecular level.

“A normal cell grows for just the right amount of time that is required for us to develop and maintain our bodies,” explains associate professor Oliver Rackham, of the University of Western Australia in Crawley.

Certain molecular mechanisms are in place in cells that “tell” them how much to grow and when it’s time to stop growing.

One such mechanism involves telomeres, which are the “caps” at the ends of chromosomes. Chromosomes carry genetic information.

Telomeres are “attached” to the single strands of DNA that are left “hanging” at the endings, or termini, of chromosomes, securing them, as it were.

“[Cells] control their growth with a molecular counting mechanism that tells the cell how old it is. This occurs on the ends of our chromosomes which have little caps on them,” Rackham says.

“Each time the cell divides,” he goes on, “a little bit at the cap of the chromosome disappears. Once the caps shrink to a certain length the cell knows that it has divided too many times and it will then stop growing or die.”

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How cancer disregulates cell growth

But problems occur when the telomeres don’t shorten incrementally, as they ought to. Throughout a person’s childhood, telomeres are naturally “longer-lived,” as the individual still needs to grow and develop.

However, if, in adulthood, the mechanism that regulates the shortening of telomeres and thus the aging process of cells is disrupted and telomeres do not shorten, the cells keep growing abnormally.

This, research has shown, is what happens in cancer. As Rackham puts it, “[C]ancer cells subvert the counting mechanism that shrinks the ends of our chromosomes so cancer cells keep replicating indefinitely.”

How does cancer “hijack” telomeres? “[B]y producing an enzyme called telomerase which we need when we are babies and growing very fast but which we stop producing when we stop rapidly growing,” explains Rackham.

Approximately 90 percent of all cancer cells contain telomerase, thus disrupting the normal cellular self-regulating mechanism, notes the researcher.

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These artificial proteins are a ‘first’

Rackham and a team of specialists from the University of Western Australia’s Harry Perkins Institute of Medical Research have been working to find an effective way to stop telomerase from facilitating the abnormal growth of cells in cancer.

This enzyme works by “lengthening” the telomeres that at the ends of chromosomes, practically “renewing” their lease of life.

As they reported in an article that is now published in the journal Nature Communications, the University of Western Australia team has developed artificial proteins that wrap around the ends of chromosomes, thus preventing telomerase to “reinforce” the telomeres.

“These proteins,” explains Rackham, “lock down the [single-stranded] DNA [which is secured by telomeres] so telomerase can’t touch it.”

“Our laboratory designed proteins that, for the first time, can actually recognise the single-stranded DNA and bind it. We can basically program these proteins to target them,” he notes.

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In doing this, the team managed to disrupt the molecular mechanism that cancer would “hijack” in order to fuel the uncontrolled, and thus harmful, growth of cells.

The researchers have expressed their excitement at their discovery, arguing that the development of proteins able to bind to single-stranded DNA could, in the future, be used in multiple areas of therapeutic interest.

“In this study we have shown that we have the ability to design proteins that recognise specific [single-stranded DNA] sequences of interest, with many potential applications in biology and biotechnology,” the authors conclude.

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