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Cancer researchers have identified a new molecular mechanism that causes cells to grow faster than they normally do. Importantly, they also discovered how to turn the mechanism into a weapon against cancer cells.
The latest study, conducted by scientists from the Genome Institute of Singapore (GIS) at the Agency for Science, Technology and Research (A*STAR), the University of Oxford, and the MD Anderson Cancer Center at the University of Texas, reveals how methylation marks1 on the transcription factor2 E2F can influence the growth properties of cells. They also found that the reprogramming of these marks could activate the "suicide machinery" in rapidly growing cancer cells.
The results have led to a better understanding of the molecular basis behind cancer growth and the information generated could prove vital to clinical applications, especially in the development of more effective anti-cancer drugs.
The findings from this study were published on 11th October 2013 in the scientific journal Molecular Cell.
Dr Shunsheng Zheng, a Graduate Scholar under the joint A*STAR-Oxford DPhil training program and first author of the study said, "E2F has been described as a 'Jekyll-and-Hyde' protein due to its ability to morph between pro-life and pro-death versions."
Professor Nick La Thangue of the Department of Oncology at Oxford University, who supervised the project, explained: "It's like there's an angel and a devil competing to get on each shoulder of the protein. Which one gets the upper hand is able to whisper in the ear of the protein and tell it what it should do. With the molecular flag on one shoulder, E2F goes into cell kill mode. With the flag on the other, it goes into cell growth mode."
The transcription factor E2F is a DNA-binding protein that controls the expression of genes required for cell growth. In some situations, such as cancer, increased E2F activity causes cells to grow at an accelerated rate. Incidentally, E2F activity can also be manipulated to activate genes involved in a form of cell death known as apoptosis.
Prof Qiang Yu, Senior Group Leader at the GIS, who was involved in this discovery, said, "Our study reveals a novel mechanism for fine-tuning cancer cell fate decision. As E2F pro-apoptotic activity in cancer cells is tightly regulated, this finding may provide a therapeutic opportunity to push cancer cells for apoptosis by modulating the methylation markers of E2F."
Prof Huck Hui Ng, Executive Director at the GIS said, "This study provides a successful example of the joint A*STAR-Oxford graduate program and highlights the importance for international collaboration. Both teams have a long-standing common interest in cancer cell fate regulation and this collaboration provides a new level of understanding of cancer cell death and survival."
Sir David Lane, A*STAR Chief Scientist and Scientific Director of the Ludwig Institute of Cancer Research said: "This is a wonderful example of the power of effective collaboration and the detailed study of protein modifications is proving to be a very fertile area for the discovery of effective new targets for cancer drug discovery."
The international team of researchers was supported by grants from A*STAR Singapore, Cancer Research UK (CRUK), Medical Research Council UK, National Institutes of Health (NIH), Cancer Prevention Research Institute of Texas and the Center for Environmental and Molecular Carcinogenesis at MD Anderson.
1 Methylation is a biochemical process involving the addition of a methyl group to a substance. A methyl group consists of a carbon atom fused with three hydrogen atoms.
2 A transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to messenger RNA.
Authors: Shunsheng Zheng, Jutta Moehlenbrink, Yi-Chien Lu, Lykourgos-Panagiotis Zalmas, Cari A. Sagum, Simon Carr, Joanna F. McGouran, Leila Alexander, Oleg Fedorov, Shonagh Munro, Benedikt Kessler, Mark T. Bedford, Qiang Yu, Nicholas B. La Thangue
Molecular Cell - doi.org/10.1016/j.molcel.2013.08.039
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Genome Institute of Singapore. "'Jekyll-and-Hyde' protein determines life and death of cancer cells." Medical News Today. MediLexicon, Intl., 9 Oct. 2013. Web.
4 Dec. 2013. <http://www.medicalnewstoday.com/releases/267124>
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