Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

'Jekyll and Hyde' Protein Offers New Route to Cancer Drugs

Published: Friday, September 27, 2013
Last Updated: Friday, September 27, 2013
Bookmark and Share
The mood changes of a 'Jekyll-and-Hyde' protein, which sometimes boosts tumour cell growth and at other times suppresses it, have been explained.

The researchers in Britain, with collaborators in Singapore and the USA, carried out a comprehensive biological study of the protein E2F, which is abnormal in the vast majority of cancers. They were able to explain the dual natures it can take up in cells in the body, and indicate how it could be a potent target for developing new cancer drugs.

The Oxford University scientists have since carried out a drug-discovery screen, and shown that compounds which block the protein’s change into 'Mr Hyde' result in the death of cancer cells.

'This mechanism for switching a key protein is very novel. Nothing else I’ve come across behaves like it,' says Professor Nick La Thangue of the Department of Oncology at Oxford University, who led the work. 'Subtle changes in terms of the chemistry of the protein have dramatic and polar opposite effects on the tumour cell, either allowing them to continuously grow or switching them to cell death mode.

'We are excited by this new discovery, which provides a new and very important approach to developing new types of cancer drugs. We have much work to do,' says Professor La Thangue.

The researchers from the University of Oxford, the Genome Institute of Singapore and the University of Texas' MD Anderson Cancer Centre in the USA report their findings in the journal Molecular Cell. The study was part-funded by the UK Medical Research Council and Cancer Research UK.

Cells in the body go through cycles of growth and division, pauses and death in a highly regulated way. Cancer involves the breakdown of these controls leading to unlimited expansion of the cells in a growing tumour.

The protein E2F is inextricably linked to cancer. It is normally tightly controlled in the cell cycle, but in most if not all cancer cells the processes E2F oversees go awry so that it keeps cells growing.

Puzzlingly, while it can be a factor driving cancer, on other occasions E2F is protective and removes damaged cells. When normal cells experience damage, E2F is involved in switching the cell towards cell death in a process called apoptosis. This helps prevent the build up of DNA errors and the development of cancer.

It’s this dual Jekyll-and-Hyde nature of E2F that the researchers have been able to explain for the first time.

They show that E2F is an important switch that determines cell fate. As Dr Jekyll, when DNA damage is detected, it leads to cell death. As Mr Hyde, it switches on cell growth and proliferation – and in most if not all cancers, it is this function of E2F that becomes out of control.

The researchers show that two enzymes compete to attach a molecular label, or flag, on different parts of the E2F protein. The flag in one position sees E2F act to cause cell death and the same flag in another position see E2F boost cell growth and proliferation.

Professor La Thangue says: '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 challenge is to mimic this process with drugs, and reinstate the death pathway in tumour cells.'

In cancer cells, E2F gets stuck with the flag boosting growth and division, helping drive the tumour's growth. The researchers identified another protein in the cell which looks for the presence of this flag.

'Blocking this protein means the devil's whispers never get heard and E2F doesn't transform into Mr Hyde,' says Professor La Thangue. 'Instead, E2F switches over to cell-death mode and the cancer cells die out.

'We've identified compounds – drug candidates - that do exactly that,' he explains.

Dr Shunsheng Zheng, first author of the study and a graduate student on the joint A*STAR-University of Oxford DPhil scholarship programme, said: 'E2F is a tricky protein to work with. Normal cells use it for growth, cancer cells need it for hypergrowth, but too much of it seems to drive cancer cells into suicidal mode.'

Dr Kat Arney, science information manager at Cancer Research UK, which part-funded the work, said: 'Cancer is a complex biological problem, and getting to grips with the molecules that drive it is essential if we're to find new cures. Although there's a lot more work to be done before this new discovery could become a treatment for patients, this research is an important step forward in understanding E2F’s "split personality" in both driving and destroying cancer cells.'


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Genetic Research Can Significantly Improve Drug Development
With drug development costs topping $1.2bn (£850 million) to get a single treatment to the point it can be sold and used in the clinic, could genetic analysis save hundreds of millions of dollars?
Friday, June 17, 2016
Genes That Increase Children's Risk Of Blood Infection Identified
A team led by Oxford University has identified genes that make certain children more susceptible to invasive bacterial infections by performing a large genome-wide association study in African children.
Friday, May 27, 2016
Origin of a Species
A study by researchers at the Wellcome Trust Centre for Human Genetics at Oxford University has uncovered the key role played by a single gene in how groups of animals diverge to form new species.
Monday, February 15, 2016
Identifying Drug Resistance Traits
Scientists have developed an easy-to-use computer program that can quickly analyse bacterial DNA from a patient's infection and predict which antibiotics will work, and which will fail due to drug resistance.
Tuesday, December 22, 2015
Faster, Cheaper TB Diagnosis
Whole Genome Sequencing is a faster, cheaper and more effective way of diagnosing tuberculosis says a new study.
Wednesday, December 09, 2015
Why we Still Don’t Have Personalised Medicine
15 years after sequencing the human genome we still do not have the promised personalised medicine, why is this?
Friday, December 04, 2015
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Tuesday, November 24, 2015
Mini DNA Sequencer’s Data Belies its Size
A miniature DNA sequencing device that plugs into a laptop and was developed by Oxford Nanopore has been tested by an open, international consortium, including Oxford University researchers.
Tuesday, October 20, 2015
New Insight into Recombination and Sex Chromosomes
Not only does the platypus have some odd physical features, an updated version of its genome has also underscored the unusual genetic characteristics that it harbors.
Tuesday, May 12, 2015
Protein Clue To Sudden Cardiac Death
A protein has been shown to have a surprising role in regulating the 'glue' that holds heart cells together, a finding that may explain how a gene defect could cause sudden cardiac death.
Tuesday, February 17, 2015
Investment In Cancer Research At Oxford University
Centre for Molecular Medicine to focus on cancer genomics and molecular diagnostics, through a partnership with the Chan Soon-Shiong Institute.
Friday, October 24, 2014
Genetic Tracking Identifies Cancer Stem Cells in Patients
The gene mutations driving cancer have been tracked for the first time in patients back to a distinct set of cells at the root of cancer – cancer stem cells.
Friday, May 16, 2014
Eating Organic Food Doesn't Lower Overall Cancer Risk
Women who always or mostly eat organic foods have the same likelihood of developing cancer as women who eat conventionally produced foods.
Tuesday, April 01, 2014
New Trial of Personalized Cancer Treatment Begins in Oxford
Phase I trial in Oxford will investigate a new drug, called CXD101.
Tuesday, March 18, 2014
Interactive Map of Human Genetic History Revealed
Study identifies, dates and characterizes genetic mixing between populations.
Tuesday, February 18, 2014
Scientific News
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Revealing the Genetic Causes of Bowel Cancer
A landmark study has given the most detailed picture yet of the genetics of bowel cancer — the UK's fourth most common cancer.
The Epigenetic Influences of Chronic Pain
Researchers at Drexel University College of Medicine are aiming to identify new molecular mechanisms involved in pain.
Fighting Resistant Blood Cancer Cells
Biologists present new findings on chronic myeloid leukemia and possible therapeutic approaches.
Tumor Cells Develop Predictable Characteristics
Scientists have discovered that cancer cells at the edge of a tumor that are close to the surrounding environment are predictably different from the cells within the interior of the tumor.
Mothers Obesity Could be Passed on in mtDNA
Obesity can predispose offspring in multiple generations to metabolic problems.
New Imaging Method Reveals Nanoscale Details about DNA
Enhancement to super-resolution microscopy shows orientation of individual molecules, providing a new window into DNA’s structure and dynamics.
Genetic Research Can Significantly Improve Drug Development
With drug development costs topping $1.2bn (£850 million) to get a single treatment to the point it can be sold and used in the clinic, could genetic analysis save hundreds of millions of dollars?
Naked Mole Rat Exhibits “Extraordinary” Cancer Resistance
Scientists are getting closer to understanding the anti-cancer mechanism of the naked mole rat by making induced pluripotent stem cells.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!