Harvard researchers have examined the factors that help spur the progression of colorectal cancer and identified the integrin [alpha]v[beta]6 as an important risk factor for development of early-stage disease. They further demonstrate that detection of high levels of this molecule is able to predict patient survival for colorectal cancer, a disease that kills over 55, 000 Americans each year. The study will appear online on January 20 in advance of publication in the February 1 print edition of the Journal of Clinical Investigation.
During embryonic development or wound repair, epithelial cells that line cavities within the body often undergo a change of shape and function in a process known as epithelial-mesenchymal transition (EMT). On occasion, this transition can result in the conversion of epithelial cells to tumor cells.
Richard Bates and colleagues, interested in determining what factors disrupt normal EMT and drive the development of tumor cells, examined the EMT process in colon carcinoma cells. They found that EMT involves activation of the protein integrin known as [alpha]v[beta]6 and this protein enhances the tumor-generating properties of these cells. Furthermore, analysis of almost 500 human colorectal carcinoma samples revealed that elevated levels of [alpha]v[beta]6 expression were associated with a significantly reduced survival time of patients in comparison with tumors that express little or low levels of this molecule.
The results define [alpha]v[beta]6 expression as an independent prognostic marker for colorectal cancer and, most significantly, one that is predictive of the outcome of early-stage disease.
TITLE: Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma