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Good indicator of cancer prognosis turned on its head by new research

Date:
July 7, 2016
Source:
Manchester University
Summary:
A molecule which, for the last 20 years has been believed to be an indicator of good prognosis in tumors, has been shown to have a dark side, scientists report.
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A molecule which, for the last 20 years has been believed to be an indicator of good prognosis in tumors has been shown to have a dark side by new research from The Universities of Manchester, Athens and collaborators, recently published in Nature Cell Biology.

The molecule p21WAF1/Cip1 (or p21 for short) is often found in association with a so-called 'master tumor-suppressor' p53. This has traditionally given doctors an indication that there is a good prognosis for cancer -- the presence of p21 indicating that the p53 tumor suppressor will lead to a less aggressive tumor.

However, the new study has presented evidence that turns this assumption on its head. Scientists at The University of Manchester, part of the Manchester Cancer Research Centre, alongside international collaborators, especially at the University of Athens, have shown that in tumors where the p53 molecule is deficient, p21 dramatically increases the ability of tumors to grow and spread throughout the body.

Professor Paul Townsend, one of the lead authors, along with senior author, Professor Vassilis Gorgoulis, Honorary Professor in Manchester, and Professor-Director, University of Athens, have said: "Years ago, being exposed to a lot of sunshine was thought to be one of the best ways of being healthy before we realised the harmful effects of too much could have.

"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."

The findings are a result of five years' of study into p21, originally with a view to developing treatments, which increase its presence and supress tumors. While conducting this investigation the international research team noticed that in p53-deficient tumors increased p21 was actually correlating aggressive behaviour. This led them to suspect a different possibility for how the molecule was working in tumors.

In reality, p21works by deregulating the DNA replication machinery and triggering what's called replication stress. This causes genomic instability, a key hallmark of cancer.

The new findings open up the possibility of treatments being developed which counter p21, an avenue of research which has not been previously explored.

Professors Townsend added: "We now know that p21, when unleashed from p53 control, is a factor in causing the danger signs of cell replication found in aggressive tumors. Although this goes against what we have known to date, it offers the hope of developing new treatments for cancer in the years ahead."


Story Source:

Materials provided by Manchester University. Note: Content may be edited for style and length.


Journal Reference:

  1. Panagiotis Galanos, Konstantinos Vougas, David Walter, Alexander Polyzos, Apolinar Maya-Mendoza, Emma J. Haagensen, Antonis Kokkalis, Fani-Marlen Roumelioti, Sarantis Gagos, Maria Tzetis, Begoña Canovas, Ana Igea, Akshay K. Ahuja, Ralph Zellweger, Sofia Havaki, Emanuel Kanavakis, Dimitris Kletsas, Igor B. Roninson, Spiros D. Garbis, Massimo Lopes, Angel Nebreda, Dimitris Thanos, J. Julian Blow, Paul Townsend, Claus Storgaard Sørensen, Jiri Bartek, Vassilis G. Gorgoulis. Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing. Nature Cell Biology, 2016; 18 (7): 777 DOI: 10.1038/ncb3378

Cite This Page:

Manchester University. "Good indicator of cancer prognosis turned on its head by new research." ScienceDaily. ScienceDaily, 7 July 2016. <www.sciencedaily.com/releases/2016/07/160707083256.htm>.
Manchester University. (2016, July 7). Good indicator of cancer prognosis turned on its head by new research. ScienceDaily. Retrieved April 27, 2017 from www.sciencedaily.com/releases/2016/07/160707083256.htm
Manchester University. "Good indicator of cancer prognosis turned on its head by new research." ScienceDaily. www.sciencedaily.com/releases/2016/07/160707083256.htm (accessed April 27, 2017).