Nature Cell Biology 5, pp 212 - 215

Colon cancer is the second most common cancer in the USA, with 150,000 new cases diagnosed in any year. Attempts to treat colon cancer are hampered by gaps in our understanding of its molecular basis. One of these gaps may be plugged this week by a report published in Nature Cell Biology.

All inherited colon cancers and most sporadic colon cancers have mutations in the adenomatous polyposis coli (APC) gene. Colon cancer cells can also migrate and form malignant tumours in other tissues. Now APC is clearly linked to the migration of colon cancer cells in work by Dr Tetsu Akiyama and colleagues at the Institute for Molecular and Cellular Biosciences, Tokyo, Japan in the March issue of Nature Cell Biology (5, 212–215 (2003)).

Akiyama and colleagues show that APC binds a protein, Asef, which is known to have effects on cell migration. Colon cancer cells that lack Asef do not migrate. Mutated versions of APC that are found in colon cancer tumours appear to activate Asef and increase cell migration.

For cancer cells to begin migration, they also need to reduce their adhesion to other cells, and we know that Asef also acts to weaken cell adhesion. Consistent with a role in activating Asef, colon cancer cells with truncated forms of APC enhance this lack of adhesion.

Further research is now needed to determine if the effects of truncated APC on the activity of Asef could be used to develop new treatments for colorectal carcinomas and prevent cell migration.