Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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
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 2,500+ scientific posters on ePosters
  • More Than 3,800+ 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

Funding Boost for Diabetes Research
Programme of research could be a game-changer for people with Type 1 diabetes and insulin-dependent Type 2 diabetes.
Friday, July 24, 2015
Ebola Vaccine Trial Begins in Senegal
A clinical trial to evaluate an Ebola vaccine has begun in Dakar, Senegal, after initial research started at the Jenner Institute, Oxford University.
Thursday, July 16, 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
Oxford Vaccine Group Begins First Trial of New Ebola Vaccine
Oxford University doctors and scientists are starting the first safety trial of an experimental preventative Ebola vaccine regimen being developed by the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen).
Wednesday, January 07, 2015
New Vaccine Generates Strong Immune Response Against Hepatitis C
A new hepatitis C vaccine has shown promising results in an early clinical trial at Oxford University, generating strong and broad immune responses against the virus causing the disease.
Friday, November 07, 2014
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
A-maize-ing Double Life of a Genome
Study findings could help current efforts to improve existing crop varieties.
Tuesday, July 15, 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
UK Scientists to Begin Trial of Potential HIV Cure
Scientists and clinicians from five leading UK universities will begin a groundbreaking clinical trial next year to test a possible cure for HIV infection.
Tuesday, November 26, 2013
Nanoparticles to Probe Mystery Sperm Defects Behind Infertility
A way of using nanoparticles to investigate the mechanisms underlying 'mystery' cases of infertility has been developed.
Monday, November 18, 2013
Scientists Break Blood-Brain Barrier to Allow Cancer Drugs In
Oxford University scientists have found a way of delivering drugs more effectively to treat life-threatening cancers that have spread to the brain.
Tuesday, October 15, 2013
Scientific News
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!