Discovery of genetic pathway
impacting the spread of cancer cells

June 18, 2012 3:07 pm Views: 102
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Dr. Torchia is a Scientist at Lawson Health Research Institute and London Health Sciences Centre’s London Regional Cancer Program. He is also an Associate Professor in the Departments of Oncology and Biochemistry at Western University

One of the greatest dangers with any type of cancer is its capacity to spread. Through the emerging fields of DNA methylation and epigenetics, scientists at Lawson Health Research Institute are exploring new areas of genetics that could stop the spread right at the source.

“Methylation,” is a metabolic process that regulates cell division. It involves a series of chemical changes that modify DNA, turning genes on or off and making sure cells divide at a healthy, balanced rate. Enzymes and proteins are essential to the methylation process. These biological materials help cells run like well-oiled machines. Unfortunately, certain factors can either boost or bar their effects.

Cancer is one area where this appears to be the case. Researchers believe a genetic mechanism is throwing the methylation process off balance. This is causing the cells to resist regulation and divide uncontrollably.

While previous studies have confirmed genetics has an impact on DNA methylation, they have yet to confirm how. “This process has been referred to as enigmatic,” says Dr. Joseph Torchia, a Scientist at Lawson. “DNA methylation is a biomarker for all kinds of cancers. While the mechanism driving its appearance is well established, removal of DNA methylation at a particular place in the genome has been unclear.”

Dr. Torchia and his lab are devoted to uncovering the mysteries of DNA methylation in cancer. In a recent study published in Molecular Cell, they looked specifically at the impact of one protein: Transforming Growth Factor Beta (TGF-β). TGF-β has been known to control cell proliferation, but the exact mechanism it uses has never been identified. By analyzing the effects of TGF-β through genetic sequencing, Dr. Torchia and his group have revealed a never-before-seen pathway.

Findings show when TGF-β comes into contact with a cell, it turns on an enzymatic pathway that removes DNA methylation. This activates a tumor-suppressing gene that stops the cells from dividing. Unfortunately, some cancer causing genes can interfere with this entire process by binding to the DNA. This prevents the tumour-suppressing genes from activating, and the cells continue to divide.

“This link between reversible DNA methylation and TGF-β has never been shown before,” Dr. Torchia says. These results provide further insight into the dynamic processes underlying cell division that could provide hope for new cancer therapies.

“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,” Dr. Torchia says.

Moving forward, Dr. Torchia and his group are continuing to pursue the broader impact of TGF-β signaling. “This work certainly advances the field,” he says. “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.”

Article By:

Sonya Gilpin

Sonya Gilpin works in Communications and Public Relations at the Lawson Health Research Institute.

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