Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer


Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherentepithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cellspossessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to thecomplex architecture of the embryo by permitting the progression of embryogenesis from a simple single-celllayer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells.However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typicallymaintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and thegain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasingevidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronicinflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC).Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn’sdisease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A largebody of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivatedprotein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymaltransition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, andanalysis refered to it can yield novel targets for therapy.