Shutting Down Oral Cancer
BU team links overexpressed gene to spreading tumors| From Explorations | By Caleb Daniloff
Oral cancer, which affects the mouth and throat, can spread quickly and has a 50 percent survival rate beyond five years. But research at BU’s Henry M. Goldman School of Dental Medicine offers new insight into how the disease might be treated.
Maria Kukuruzinska, an SDM professor of molecular and cell biology, has shown a direct relationship between the aberrant behavior of a gene known as DPAGT1 and the loss of adhesion between cells in oral cancer cell lines and oral tumor tissues. In healthy tissues, cells are held together with the help of an adhesion receptor called E-cadherin. In oral cancer, the DPAGT1 gene is overactive, and interferes with E-cadherin’s adhesive properties. Tumors spread when cells can’t stick to one another.
“Such discohesive cells peel off the tumor and establish new tumor islands,” Kukuruzinska says. “The hallmark of malignancy is when cells break apart, migrate, and nest in inappropriate organs.”
When researchers suppressed DPAGT1, they enhanced the E-cadherin molecule’s ability to form junctions between cells. The team’s findings suggest that diminishing DPAGT1’s activity could interrupt the growth of a tumor.
“You can’t jump to the conclusion that you can stop cancer from developing,” says Kukuruzinska, whose study appeared in the July 15 issue of Cancer Research. “But we can perhaps stop tumors from spreading.”
Now researchers want to find the cause of the gene’s overexpression. They hope to identify repressor molecules that regulate the gene. “We believe this is not going to be restricted to oral cancer,” Kukuruzinska says, “but will be a feature common to subsets of epithelial tumors in general.”
“Oral cancer is very pernicious and deadly,” she adds. “It’s extremely painful and difficult to treat. And it’s damaging aesthetically. Once a piece of a tongue or a jaw is removed, it’s very visible.”