Colorectal cancer progression -: Integrin αvβ6 and the epithelial-mesenchymal transition (EMT)

Carcinomas, those tumors that arise from epithelial tissues, represent the most prevalent form of human malignancies. Moreover, it is the metastatic spread of these cancers, rather than the development of primary neoplasms that predominantly accounts for patient mortality. Thus, understanding the mechanisms that contribute to the process of cancer progression is of fundamental importance to designing better therapeutic strategies for treating this disease. The epithelial-mesenchymal transition (EMT), which facilitates the process by which epithelial tumors become invasive and progress towards malignant disease, provides a superb paradigm for studying such mechanisms. Using a colon carcinoma model of EMT, it was discovered that increased expression of the integrin alpha v beta 6 is elicited as a consequence of the transition. Importantly, the consequences of the elevated alpha v beta 6 expression are directly linked to both tumor cell function and to the mechanism of the EMT itself. Most significantly, increased alpha v beta 6 expression in human tumors is a prognostic variable and one that is predictive of outcome for early-stage disease. These findings reinforce the importance of the EMT event in late stage tumorigenesis, and define alpha v beta 6 as a novel therapeutic candidate for aggressive colorectal cancer.