last updated April 2013
How colon cancer spreads
Identification of the molecules that facilitate metastasis of colon cancer cells could lead to novel therapeutics
A research team led by Reiji Kannagi of the Aichi Cancer Center, Japan, has identified the molecular mechanism underlying the aggressive spread of colon cancer1. Metastasis occurs when cells become dislodged from a primary tumor and then spread through the bloodstream to other parts of the body. This process, called epithelial–mesenchymal transition (EMT), results from changes in the adhesive properties of the cells.
Kannagi and colleagues examined colon cancer cells undergoing EMT, looking at the expression of cell surface sugar molecules called glycans, which enable them to leak from blood vessels by interacting with endothelial cells in their lining. They found that expression of two glycans, called sLex and sLea, was significantly greater in cells undergoing EMT. This was associated with enhanced binding to E-selectin, a cell adhesion molecule expressed on the surface of endothelial cells.
Further experiments revealed that expression of three glycosyltransferase genes, which encode enzymes that attach glycans to the cell surface, is also elevated in cells undergoing EMT, and that their expression is regulated by the transcription factors c-Myc and CDX2.
“Our findings suggest that these glycans may be a marker for cancer cells undergoing EMT,” says Kannagi. “We expect them to provide clues to novel molecular-targeted therapy for inhibiting the spread of colon cancer.”