Source: www.bu.edu/today
Author: Caleb Daniloff

Maria Kukuruzinska, a professor and researcher at BU’s Henry M. Goldman School of Dental Medicine, 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, offering dramatic new insight into how the disease might be treated. Oral cancer, which affects the mouth and throat, can spread quickly and has a 50 percent survival rate beyond five years.

In healthy epithelial tissues, which line body cavities and form many organs, cells are held together with the help of an adhesion receptor called E-cadherin. This molecule ensures proper cell shape and function and prevents tumor spread. In oral cancer, the DPAGT1 gene is overactive, which 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 partially suppressed DPAGT1 in the oral cancer cell lines, 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,” Kukuruzinska says. “But we can perhaps stop tumors from spreading.”

Researchers want to find the cause of overexpression of DPAGT1 in oral cancer. They hope to identify key repressor molecules that regulate the gene. Similar aberrant genetic behavior was found in a Portuguese study of mammary cancer in dogs. “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 been a neglected cancer. The understanding of the molecular basis for it is not very advanced. It’s definitely enhanced by environmental agents such as tobacco and alcohol use. It’s extremely painful and difficult to treat. And it’s damaging aesthetically to a person. Once a piece of a tongue or a jaw is removed, it’s very visible.”

Kukuruzinska’s paper “Overexpression of DPAGT1 Leads to Aberrant N-Glycosylation of E-Cadherin and Cellular Discohesion in Oral Cancer” appeared in the July 15 issue of Cancer Research.