'Molecular volume control' may help combat tumours

January 5, 2017 by Chris Melvin, University of Bath

A 'molecular volume control' may one day be used to manipulate enzyme activity in order control the development and treatment of cancer, according to research at the Universities of Dundee and Bath.

The researchers have uncovered new functions of an enzyme called Dual-specificity phosphatase 5 (DUSP5), which will help scientists to better understand how tumours develop.

DUSP5 is known to switch off the activity of another enzyme, called ERK, which controls cell growth in a number of cancers, including colon, lung and melanoma. This would suggest that DUSP5 is a , but studies have also shown that increased DUSP5 activity is observed in several human cancers.

Using cell-based models, the Dundee-Bath team have shown that the loss of DUSP5 can completely stop cancer cell formation by driving ERK activation to such high levels that it engages a natural protective mechanism within cells that makes them shut down. An analogy can be made to listening to the radio and being unable to hear comfortably when the volume is turned either too low or too high. In a similar manner, it appears that increasing or decreasing DUSP5 levels in cells can push ERK activity into ranges that are either too low or too high to cause cancer growth.

Professor Stephen Keyse from University of Dundee said: "When the link between DUSP5 and ERK was established it was logically thought that it acted to suppress , but levels of DUSP5 are observed to be increased in many human tumours, which doesn't make intuitive sense.

"What we are now seeing is that DUSP5 does indeed inhibit ERK activity, but sometimes this allows cancer cells to persist and grow by preventing them from engaging natural tumour suppressive responses. This suggests that targeting DUSP5 and thus increasing the level of ERK signalling beyond a tolerable level may offer a new route for combatting the progression of some tumours."

The paper, published in Proceedings of the National Academy of Sciences, highlights the need to better understand how normal and mutant genes interact in to predict how they might develop. The next stage for the team is to look at human cancer to determine whether DUSP5 has an effect on them.

Dr Jim Caunt, from University of Bath's Department of Biology and Biochemistry, said, "These results confounded our initial predictions and show just how important it is to understand how different types of mutation cooperate to influence cancer cell behaviour. An exciting prospect raised by the study is that monitoring DUSP5 could help us predict which types of drugs could be most effective in treatment."

Explore further: Putting the brakes on cancer

More information: DUSP5 controls the localized inhibition, propagation, and transforming potential of ERK signaling, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1614684114

Related Stories

Putting the brakes on cancer

December 19, 2014
A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how it combats the ...

Active hedgehog signalling in connective tissue cells protects against colon cancer

August 8, 2016
Many types of cancer are caused by gene mutations in the signalling pathways that control cell growth, such as the hedgehog signalling pathway. A new study from the Karolinska Institutet, published in the journal Nature Communications, ...

New insights on how brain tumours spread and become resistant to therapy

September 26, 2016
Research teams from Karolinska Institutet and Uppsala University have jointly discovered that the usually protective enzyme FBW7 is commonly mutated and inactivated in childhood brain cancers causing tumors to spread and ...

Dying tumour cells release intracellular ions in a last-ditch attempt to block the immune system

September 15, 2016
Researchers at the National Cancer Institute in the USA and the Babraham Institute, UK, have discovered how a mineral ion leaked from tumour tissue as it dies acts to stop the work of anti-tumour immune cells. This discovery ...

Accumulation of a product of cell metabolism found to be linked with kidney tumor growth

August 31, 2016
Researchers funded by the Medical Research Council (MRC) have shown that when the metabolite fumarate accumulates in a hereditary form of renal cancer it leads to an epigenetic reprogramming that drives cancer, according ...

Study explains mechanisms behind glioblastoma influence on the immune system

September 12, 2016
Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international ...

Recommended for you

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018
The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of ...

FDA approves first drug for tumors tied to breast cancer genes

January 12, 2018
(HealthDay)—The U.S. Food and Drug Administration on Friday approved the first drug aimed at treating metastatic breast cancers linked to the BRCA gene mutation.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.