New genes identified that regulate the spread of cancers

Study reveals Spns2 gene as a new drug target

New genes identified that regulate the spread of cancers

Homepage_lungs.jpg
Spread of black cancer cells to mouse lungs. Left: Spns2 gene absent - fewer metastatic colonies form. Right: Spns2 gene present. Credit: Sanger Institute

Research led by the Wellcome Trust Sanger Institute has discovered a new biological target for drugs to reduce the spread of tumours in cancer patients. Published in Nature today (11 January 2017), the study with genetically modified mice found 23 genes that are involved in regulating the spread of cancers. The researchers showed that targeting one of these genes – Spns2 – led to a three-quarters reduction in tumour spread.

The spread of tumours – metastasis - to other sites in the body is the leading cause of death for cancer patients. Up to 90 per cent of cancer deaths are due to this, however the process that regulates the spread of tumours is very poorly understood.

To find out what genes in the body could influence metastasis, the researchers looked at how tumours spread in genetically engineered mice that were missing specific single genes. They screened 810 unique genes and identified 23 genes that either increased or decreased the spread of skin tumour cells to the lungs. Many of these genes also caused an alteration in the immune system, such as changing the bodies’ ability to fight infection.

Removal of the Spns2 gene caused the largest change, reducing spread of tumours to the lungs by approximately four times. The researchers then looked at the effect of this gene on the spread of other cancers, from colon, lung and breast, and showed that taking out Spns2 also reduced the metastasis of these cancers.

“Loss of the Spns2 gene causes the greatest reduction in the formation of tumour colonies and represents a novel therapeutic target. We found that mice lacking Spns2 have a different ratio of immune system cells than normal, which seems to prime the immune system to remove cancer. Drugs that target this could help reduce or prevent the spread of tumours through the body.”

Dr David Adams from the Wellcome Trust Sanger Institute

Before this study, the Spns2 gene was known to affect the immune system, but was not implicated in tumour spread. It codes for a protein that transports a lipid, S1P, which signals to the immune system. Without this transporter protein, the signaling doesn’t work properly and results in changes in the proportion of different immune cells in the body.

“This work supports the emerging area of immunotherapy, where the bodies’ own immune system is harnessed to fight cancer. Drugs could be designed to bind to the S1P transporter, preventing it from working and causing advantageous changes to the immune system. Investigation of further targets in the Spns2 pathway, or other targets identified in this study could help develop potential therapies.”

Dr Anneliese Speak from the Sanger Institute

“This study in mice gives a new insight into the genes that play a role in cancer spreading and may highlight a potential way to treat cancer in the future. Cancer that has spread is tough to treat, so research such as this is vital in the search for ways to tackle this process.”

Dr Justine Alford, Cancer Research UK’s senior science information officer

Notes to Editors
Publications
  • Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.

    van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H et al.

    Nature 2017;541;7636;233-236

Funding:

This work was supported by Cancer Research UK and the Wellcome Trust.

Selected Websites
Is cancer a genetic disease?FactsIs cancer a genetic disease?
Cancer is the most common human genetic disease. The transition from a normal cell to a malignant cancer is driven by changes to a cell’s DNA, also known as mutations.

Role of Cancer GenesVideoRole of Cancer Genes
This flash animation shows you how DNA mutations are involved in the development of cancer. 

Pharmacogenomics and cancerStoriesPharmacogenomics and cancer
Pharmacogenomics is a specific kind of genetic testing that offers key advantages for doctors trying to choose the best drugs for their patients. 

Contact the Press Office

Dr Samantha Wynne, Media Officer

Tel +44 (0)1223 492 368

Emily Mobley, Media Officer

Tel +44 (0)1223 496 851

Wellcome Sanger Institute,
Hinxton,
Cambridgeshire,
CB10 1SA,
UK

Mobile +44 (0) 7900 607793

Recent News

2019 Chief Medical Officer’s Report published
Sanger Institute researchers contribute to Professor Dame Sally Davies' eleventh annual report
Multi-drug resistant malaria spreading in Asia
Study reveals importance of ongoing genomic surveillance for malaria control strategies
Low doses of radiation promote cancer-capable cells
New research in mice helps to understand the risks around exposure to low doses of radiation, such as CT scans and x-rays