Pathway to colon cancer progressionDec. 1, 2011, 5:08 PM
Identifying the molecular pathways that lead normal colon cells to become cancer cell could provide much needed biomarkers and therapeutic targets. Previously, Punita Dhawan, assistant professor of surgery, and colleagues showed that claudin-1—a protein member of “tight junctions” that help bind cells together into an organized tissue structure—was greatly increased and mislocalized in colorectal cancer.
In a recent report in Gastroenterology, they describe the cellular pathway by which claudin-1 influences the transition of normal colon cells into cancerous ones. They show that increased claudin-1 expression in colon cancer cells is associated with loss of expression of the epithelial cell marker E-cadherin, whose reduced expression is correlated with poor prognosis and survival in colon cancer patients. Cell experiments showed that claudin-1 modulates expression of another protein, ZEB-1, which in turn affects E-cadherin expression. This chain of events then leads to cellular changes associated with invasion and progression in colon cancer cells.
The results suggest that ZEB-1, E-cadherin and claudin-1 could serve as biomarkers to indicate invasiveness and prognosis in colorectal cancer.
The research was supported by grants from the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Disorders.