One of the greatest dangers with any type of cancer is its ability to spread. Quickly.
Through the emerging fields of DNA methylation and epigenetics, Schulich School of Medicine & Dentistry professor Joseph Torchia is exploring new areas of genetics that could stop the spread right at the source and lead to new avenues for treatment.
“If we understand how methylation is regulated, and identify the machinery that’s involved, we may be able to target some of the machinery therapeutically and turn these genes back on to fight the cancer,” he said.
Methylation is a metabolic process that regulates cell division. It entails a series of chemical changes that modify DNA, turning genes on or off and ensuring cells divide at a healthy, balanced rate. Enzymes and proteins are essential to the methylation process as these materials keep the cell running like a well-oiled machine.
Unfortunately, certain factors – like cancer – can either boost or bar their effects.
Researchers believe a genetic mechanism throws the methylation process off balance, causing the cells to resist regulation and divide uncontrollably.
“The hallmark feature of all cancers is deregulated methylation. It’s well understood how methylation occurs but the removal of the methyl mark has really been quite enigmatic,” said Torchia, a scientist at London Health Science Centre’s Regional Cancer Program. “We want to remove it from genes that are turned off. A lot of these tumour supressors, which are sort of like braking mechanism in telling cells to stop dividing, are turned off. We want to turn them on.”
In a recent study, published this past month in Molecular Cell, the Oncology and Biochemistry professor and his lab looked specifically at the impact of one protein: Transforming Growth Factor Beta (TGFB), known to control cell production. But the exact mechanism it uses has never been identified.
Findings showed when TGFB comes in contact with a cell it removes the DNA methylation, which then activates a tumour-surprising gene that stops the cells from dividing. Unfortunately, some cancer genes can interfere with this process by binding to the DNA, which prevents the tumour-supressing genes from activating and the cells continue to divide.
“We never really understood how these things are dynamically regulated, how the methylation actually occurs or is removed,” Torchia said, adding the link between methylation and TGFB has never been shown prior to this study. “If we can identify the mechanism or the components involved in removing this, we may be able to manipulate it in some way that will allow us to selectively turn on specific genes that are permanently silenced by the cancer.”
While it is still early in the process, Torchia said these results provide further insight in the dynamic processes underlying cell division that could provide hope for new cancer therapies.
Moving forward, Torchia and his group are continuing to pursue the broader impact of TGFB signaling.
“This work certainly advances the field,” he said. “We’re now using functional genomic approaches – next generation sequencing, for example – to identify other genes where this mechanism is functional and get a real big picture as to what’s going on in the cell.”