7th October 2013 - 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 marks[1] on the transcription factor[2] 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.
Research publication
The research findings described in the press release was published in the 11th October 2013 issue of Molecular Cell under the title “Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1”.
Authors:
Shunsheng Zheng•r, Jutta Moehlenbrink•, Yi-Chien Lu•, Lykourgos-Panagiotis Zalmas•, Cari A. Sagum*, Simon Carr•,Joanna McGouranº, Leila Alexander?, Oleg Fedorov?, Shonagh Munro•, Benedikt Kesslerº, Mark T. Bedford*, Qiang Yur and Nicholas B. La Thangue•
• Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK,
? Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford, OX3 7DQ, UK
* Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Centre, Smithville, Texas, USA rCancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology, and Research), Biopolis, Singapore 138672, Republic of Singapore
º Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive Oxford OX3 7FZ
- Corresponding author: Prof Nick La Thangue, Email: nick.lathangue@oncology.ox.ac.uk. Tel: 0044 1865 617090 Contact
Winnie Lim
Genome Institute of Singapore
Office of Corporate Communications
Tel: (65) 6808 8013
Email: limcp2@gis.a-star.edu.sg
Genome Institute of Singapore (GIS)
The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine.
The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Developmental Biology, Cancer Stem Cell Biology, Genomic Technologies, Computational and Systems Biology, and Translational Technologies.
The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact. www.gis.a-star.edu.sg
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.
From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.
A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions. v
About the Journal
Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and …
View full aims and scope
Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly, Molecular Cell defines the field of molecular biology with a relatively small number of significant papers, up to 15 articles per issue. Coverage will extend from structure to human diseases, concentrating on molecular analyses. Topics that will be represented in the first issues include gene expression, RNA processing, replication, recombination and repair, structure, chaperones, receptors, signal transduction, cell cycle, and tumorigenesis.
The majority of papers published in Molecular Cell are articles in the format familiar from Cell. However, we will also publish short papers (up to 6 published pages) that make focused contributions on points of general interest. The publication schedule will be rapid: on our regular monthly schedule, publication time should average 6 weeks from acceptance. Visit the Molecular Cell website to find out more - http://www.molecule.org/
About the A*STAR Graduate PhD Scholarship
The A*STAR - University of Oxford Partnership DPhil Programme (AOP) is a four-year scholarship comprising two years of DPhil studies at University of Oxford, and two years at an A*STAR Research Institute (RI) in Singapore. DPhil research training will be carried out under the supervision of senior scientists from University of Oxford and an A*STAR RI. Successful students will be conferred a DPhil degree by the University of Oxford. A*STAR Graduate Scholarship provides 4 years funding for DPhil.
Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.
In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore’s manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.
A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR’s research entities as well as a growing number of corporate laboratories.
www.a-star.edu.sg
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