March 16, 2012

Colon cancer’s cellular crossroads

New information about signaling pathways involved in colorectal cancer could aid in assessing prognosis and identifying new therapeutic targets for the disease.

(Wellcome Images)

Colon cancer development and progression involves alterations in several cell signaling pathways. Activation of the Wnt pathway is involved in the early stages of tumor development, while inactivation of signaling through the TGF-beta pathway (which typically suppresses tumor formation) is involved in later stages. However, the interactions between these pathways remain unclear.

R. Daniel Beauchamp, John Clinton Foshee Distinguished Chair in Surgery, and colleagues investigated these interactions in human colorectal cancer samples, cell lines, and a mouse model of colon cancer. In a study published in the March issue of Gastroenterology, they show that reduced levels of Smad4 (a component of the TGF-beta pathway) correlated with increased levels of beta-catenin (a Wnt pathway component) in human colon cancers. In cell lines, depletion of Smad4 also increased beta-catenin and Wnt signaling. Similar interactions were found in intestinal tumors of mice.

The findings provide important information about the interaction among these signaling pathways, which could aid in assessing prognosis and identifying new therapeutic targets for colorectal cancer.

The research was supported by grants from the National Cancer Institute, the National Institute of General Medical Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources of the National Institutes of Health.