Molecule thought to indicate good cancer prognosis not always good

When the molecule p21 is not in the presence of another molecule called p53, it can cause further growth and spreading of cancer -- contrary to two decades of research.
By Stephen Feller   |   July 7, 2016 at 4:35 PM

MANCHESTER, England, July 7 (UPI) -- Although a molecule present in some tumors often indicates a good prognosis, in the absence of another molecule it can make tumors grow and spread faster.

The molecule p21WAF1/Cip1, or p21, is often found in the presence of another molecule, p53, a "master tumor suppressor," but without it p21 can influence growth typical of more aggressive tumors, according to a new study published in the journal Cell Biology by researchers at the University of Manchester.

The molecule has been considered a good sign for cancer patients for last two decades, with researchers looking at how to increase its presence when treating tumors. The new understanding is shifting research to look at ways to counter the growth encouraged by the molecule, researchers say.

Although the molecule's interaction with p53 in cancer has been seen for some time as a positive thing because it appeared to help repair cell damage, when p21 is not in the presence of p53 it deregulates DNA replication causing genomic instability -- one of the hallmarks of cancer.

Previous studies years ago suggested that while some positive effects could be seen from the molecule, the molecule plays a role in a range of diseases including Alzheimer's disease, arthritis, heart failure and cancer.

"We now know that p21, when unleashed from p53 control, is a factor in causing the danger signs of cell replication found in aggressive tumor," Paul Townsend, a professor at the University of Manchester said in a press release. "Although this goes against what we have known to date, it offers the hope of developing new treatments for cancer in the years ahead."

Researchers at the University of Manchester have spent the last five years searching for ways to increase p21's presence in tumors to suppress their growth. During their studies, the researchers found tumors with lower levels of p53 higher levels of p21 appeared to contribute to the growth of tumors, rather than limiting their spread.

The focus of researchers now, they say, is to find ways to limit actions of the molecule, which had not previously been looked at in any of their work.

"Years ago, being exposed to a lot of sunshine was thought to be one of the best ways of being healthy before we realized the harmful effects of too much could have," Townsend said. "This protein has a similar effect. When the activity of wild type p53 is lost, excess production of p21 is far from a good thing. This protein which was previously thought benign turns out to have a dark side."

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