Scientists confirm that gene suppresses liver tumours
Scientists have confirmed that a gene called DLC1 is a 'tumour suppressor' gene, and that damage to this gene can lead to liver cancer.
The discovery paves the way for new anti-cancer treatments which target cancer-promoting molecules that are activated when the gene is switched off.
DLC1, which is so named because researchers had an idea that it was 'Deleted in Liver Cancer', is located in a region of DNA that has previously been shown to be missing in mammalian liver cancer cells.
- Dr Scott Lowe, Cold Spring Harbour Laboratory
Research published in the journal Genes and Development has now confirmed that loss or inactivation of DLC1 leads to the development of an aggressive form of liver cancer.
Dr Scott Lowe, a researcher at Cold Spring Harbour Laboratory (CSHL), revealed that the region of DNA on which DLC1 is located is large and may therefore harbour more than one tumour suppressor gene.
"We set out to conclusively identify DLC1 as a tumour suppressor, which had not been done before, and to show at the molecular level how the absence of this gene?can lead to liver cancer," he explained.
"Interestingly, loss of DLC1 is observed in a range of epithelial cancers, which suggests that DLC1 may play a common role in many types of human cancer," he noted.
The team confirmed DLC1's role as a tumour suppressor by carrying out studies on mice which had been implanted with modified liver cells in which DLC1 was absent.
Nearly all of the mice developed liver cancer, and the researchers showed that the disease could be halted by reintroducing DLC1.
Furthermore the researchers found that reduced levels of DLC1 protein result in the triggering of a complex series of events. Key amongst these is the release of an essential molecule called RhoA.
RhoA was found to kick-start liver tumour growth and the researchers showed that it is required for tumour formation.
"This suggests an opportunity for molecularly targeted therapies," said Dr Lowe. "For a variety of reasons, tumour suppressors like DLC1 are not amenable to direct therapeutic targeting. But we may be able to readily target cancer-promoting molecules like RhoA that are 'downstream' in the signalling cascade.
"Our data show that RhoA is required for maintenance of at least some tumours driven by DLC1 loss, and also that cells with disabled DLC1 are particularly sensitive to inhibitors that target at least one of the molecular 'effectors' that renders RhoA active," he continued.
"We know that DLC1 is frequently lost in human epithelial cancers. This suggests that drug intervention in the signalling pathways modulated by DLC1 may have broad therapeutic utility."